Compounds and methods for targeting pathogenic blood vessels

ABSTRACT

The disclosure provides compounds, and compositions, including pharmaceutical compositions, kits that include the compounds, and methods of using (or administering) and making the compounds. The disclosure further provides compounds or compositions thereof for use in a method of modulating PLXDC1 (TEM7) and/or PLXDC2 or killing pathogenic blood vessles. The disclosure further provides compounds or compositions thereof for use in a method of treating a disease, disorder, or condition that is mediated, at least in part, by PEDF receptors or by angiogenesis.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.62/916,983 filed on Oct. 18, 2019, which is incorporated herein byreference in its entirety.

FIELD

The present disclosure relates generally to small molecules that targetpathogenic blood vessels, compositions comprising the same, and methodsof using the compounds and compositions for treating cancer and otherpathogenic blood vessel disorders.

BACKGROUND

Angiogenesis plays a key role in the pathogenesis of several major humandiseases. In addition to tumor growth and metastasis, angiogenesis is amajor driving force in several blinding diseases including diabeticretinopathy, age-related macular degeneration (AMD), and retinopathy ofprematurity. AMD and diabetic retinopathy are the leading causes ofblindness in the elderly and populations at the working age in theUnited States, respectively. Retinopathy of prematurity is a commonreason that causes the loss of vision for newborn babies.

Angiogenesis also plays a role in pathogenesis of cancer, e.g., tumordevelopment, since newly-formed blood vessels supply the tumor withgrowth nutrients and signals that allow the tumor to grow and spread.Accordingly, cutting off a tumor's supply of nutrients and primarymechanism for traveling to distant sites is an attractive therapeuticstrategy. However, current anti-angiogenic strategies only target newlyformed blood vessels, and are unable to target existing blood vesselsthat contribute to disease progression.

Different disease progression patterns can be induced by anti-angiogenictherapies, which may lead to worse outcomes in terms of drug resistance,invasion, and metastasis. Furthermore, targeting angiogenesis does nottreat existing blood vessels that may have, for example, alreadyvascularized a tumor. There is a need in the art for complementarytherapies that, in contrast to anti-angiogenic therapies, can targetexisting blood vessels and treat cancer and other disorders arising fromangiogenesis (collectively referred to herein as pathogenic blood vesseldisorders).

SUMMARY

The disclosure provides compounds, and compositions, includingpharmaceutical compositions, kits that include the compounds, andmethods of using (or administering) and making the compounds. Thedisclosure further provides compounds or compositions thereof for use ina method of modulating PLXDC1 (TEM7) and/or PLXDC2 or killing pathogenicblood vessles. The disclosure further provides compounds or compositionsthereof for use in a method of treating a disease, disorder, orcondition that is mediated, at least in part, by PEDF receptors or byangiogenesis.

In certain embodiments, provided are compounds of Formula (I) or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereinFormula (I) is

wherein each of n, R¹, R², R⁵, R⁶, R⁷, R⁸ and R⁹ is as defined herein.

In certain embodiments, provided is a pharmaceutical compositioncomprising a compound as described herein, or a pharmaceuticallyacceptable salt, isotopically enriched analog, stereoisomer, mixture ofstereoisomers, or tautomer thereof, and a pharmaceutically acceptablecarrier.

In some embodiments, the compound activates the PLXDC (e.g., PLXDC1and/or PLXDC2) protein. In some embodiments, the compound induces NFκBactivation. In some embodiments, the compound induces NFκB activation inpathogenic blood vessels. In some embodiments, the compound increasesnecrosis of pathogenic blood vessels. In some embodiments, thepathogenic blood vessel-related disorder comprises diabetic retinopathy,age-related macular degeneration (AMD), retinopathy of prematurity, orcancer. In some embodiments, the pathogenic blood vessel-relateddisorder comprises cancer. In some embodiments, the cancer comprisescolon cancer. In some embodiments, the cancer comprises lung cancer. Insome embodiments, the cancer comprises a solid tumor. In someembodiments, the cancer comprises a vascularized tumor.

In some embodiments, the pathogenic blood vessel-related disordercomprises cancer and further wherein the patient is one that has amalignant tumor. In some embodiments, the tumor comprises a solid tumor.In some embodiments, the tumor has a diameter of greater than 2 cm. Insome embodiments, the tumor has a diameter of at least, or at most 1, 2,3, 4, 5, 6, 7, or 8 cm (or any range derivable therein).

In some embodiments, the compound specifically induces endothelial cellnecrosis in the targeted blood vessels. In some embodiments, thecompound does not directly induce tumor cell necrosis. In someembodiments, the compound induces and/or increases coagulative necrosisin a tumor in the patient. In some embodiments, the compound inducesand/or increases infarction in the tumor. In some embodiments, thepatient has been determined to have pathogenic blood vessels. In someembodiments, the patient has been determined to have PLXDC1 and/orPLXDC1-expressing cells. In some embodiments, the expressing cellscomprise endothelial cells. In some embodiments, the expressing cellscomprise cell surface expression of PLXDC1 and/or PLXDC2.

In some embodiments, the patient has previously been treated for thepathogenic blood vessel-related disorder with an additional therapy. Insome embodiments, the patient has been determined to be non-responsiveor have a toxic response to the additional therapy. In some embodiments,the additional therapy comprises an anti-angiogenic therapy. In someembodiments, the additional therapy comprises an immunotherapy. In someembodiments, the patient has not previously been treated for thepathogenic blood vessel-related disorder.

In certain embodiments, provided is a method for treating a disease ordisorder that is mediated, at least in part, by PLXDC1 and/or PLXDC2 ina subject in need thereof, the method comprising administering to thesubject an effective amount of a compound or a pharmaceuticalcomposition comprising a compound as described herein, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof.

The disclosure also provides uses of the compounds, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, in themanufacture of a medicament for modulating PLXDC (e.g., PLXDC1 and/orPLXDC2). Moreover, the disclosure provides uses of the compounds, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, in themanufacture of a medicament for the treatment of a disease, disorder, orcondition that is mediated, at least in part, by PLXDC1 and/or PLXDC2.

The disclosure also provides use of the compounds, or a pharmaceuticallyacceptable salt, isotopically enriched analog, stereoisomer, mixture ofstereoisomers, or tautomer thereof, in treating a disease, such ascancer, retinal occlusive vascular disease, retinopathy of prematurity,diabetic retinopathy, and age-related macular degeneration.

These and other aspects of the disclosure is further described in thetexts that follow.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings form part of the present specification and areincluded to further demonstrate certain aspects of the presentinvention. The invention may be better understood by reference to one ormore of these drawings in combination with the detailed description ofspecific embodiments presented herein.

FIG. 1A-H. Expression of PLXDC1 in pathogenic blood vessels in choroidalneovascularization (CNV) and ischemia-induced retinopathy. Red channelshows blood vessel marker Griffonia simplicifolia Lectin I-isolectin B4.Green channel shows anti-PLXDC1 signal. A-D. Highly enriched PLXDC1expression in pathogenic blood vessels in a mouse model of CNV(laser-induced CNV). A&B, retina sections. Arrowheads indicate examplesof normal inner retinal blood vessels (in A) that are negative forPLXDC1 signal (in B). C&D, staining done on flat-mounted eye cup. E-H.High expression of PLXDC1 in pathogenic blood vessels in a mouse modelof ischemia-induced retinopathy, but not in blood vessels of healthyretina. E&F. P17 retina of ischemia-induced retinopathy (E and F are thesame section stained by endothelial cell marker and PLXDC1 antibody,respectively). Examples of pathogenic blood vessels expressing PLXDC1are indicated by white arrows. G&H. P17 healthy retina (G and H are thesame section stained by endothelial cell marker and PLXDC1 antibody,respectively). Examples of healthy blood vessels showing no detectablePLXDC1 expression are indicated by white arrows in G (there is nocorresponding PLXDC1 signals in H). CH, choroid. ON, outer nuclearlayer. IN, inner nuclear layer. GC, ganglion cell layer.

FIG. 2A-E. Comparison of compound 369 with the current anti-angiogenicdrug in an ex vivo model of choroidal angiogenesis. A. A schematicdiagram of the timeframe of the experiment. Treatment does not startuntil choroidal angiogenesis occurs for 7 days. Treatment lasts for twodays before cell death and survival are analyzed. B. Control experimentwithout any drug treatment at day 7. The white circle in the middledelineates the piece of choroid/RPE that was embedded to initiateneovascularization. C. The most commonly used drug for choroidalneovascularization, Eylea, can inhibit choroidal endothelial cell growth(as expected of an antiangiogenesis drug). Eylea was added at 10 μM. D.Compound 369 that targets PLXDC1/PLXDC2 can kill the new endothelialcells in choroidal angiogenesis. Choroid and RPE are still alive afterthe treatment, demonstrating the high specificity of the treatment. Thecompound was added at 10 μM. In B-D, green cells are live cells and redcells are dead cells. E. Quantitation of the experiments described inB-D. The amount of new endothelial cells in the untreated control isdefined as 100%.

FIG. 3A-B shows tumor shrinkage and necrosis following treatment withcertain compounds described herein. FIG. 3A shows that 3 days afterinjection, all the tumors were shrinking FIG. 3B shows that the tumorshrinkage was maintained 6 days after injection.

FIG. 4A-B show tumor shrinkage and necrosis following treatment withcompounds described herein. FIG. 4A shows that 3 days after injection,all the tumors were shrinking FIG. 4B shows that the tumor shrinkage wasmaintained 6 days after injection.

FIG. 5A-B show activation of PLXDC1 and PLXDC2 by small molecules.Through RNAseq analysis of PLXDC1-expressing endothelial cells killingby PLXDC1-activating compounds, a transcriptional factor called Gfi1bwas found to be induced during PLXDC1-mediated cell killing By linkingits promotor to a luciferase reporter gene, this example developed aPLXDC1 receptor activation assay that demonstrates the activation of thereceptor by its ligands. A. PLXDC1-activating compounds (A-Com-1 andA-Com-2) highly activated the promotor activity in PLXDC1-expressingcells. B. A-Com-1 and A-Com-2 also activated the promotor activity inPLXDC2-expressing cells. However, both compounds preferentially activatePLXDC1 over PLXDC2. A-Com-2 more strongly differentiates between the tworeceptors. All compound treatments were done for 1 day. Basal promotoractivity of the PLXDC1-expressing cells is defined as 1. Fluorouracil(FU), a chemotherapy drug that kills dividing cells by apoptosis, do notactivate this promotor.

FIG. 6A-B show killing of PLXDC1-expressing endothelial cells byPLXDC1-activating small molecules and antibodies. A. Visualization ofthe killing human PLXDC1-expressing endothelial cells byPLXDC1-activating small molecule (compound). The top three pictures onrepresent control cells and the lower three pictures representcompound-treated cells, showing light microscopy picture (left), livecell (middle) and dead cell staining (right). Live cells are stainedusing Fluorescein diacetate (green signal) and dead cells are stainedusing propidium iodide (red signal). B. Quantitation of the killing ofhuman PLXDC1-expressing endothelial cells by PLXDC1-activating smallmolecules (A-Compound-1 and A-Compound-2) and antibodies (A-TEM7-Ab-1and A-TEM7-Ab-2). Incubation time of the compounds and antibodies is 24hours. Cell survival of the control cells is defined as 100%.

FIG. 7A-D show that PLXDC1-activating compound specifically suppressespathogenic blood vessels in vivo without affecting healthy blood vesselsin ischemia-induced retinopathy. A. Upper graph: Schematic diagram ofthe experimental design for ischemia-induced retinopathy. The highoxygen environment caused blood vessel loss (vaso-obliteration). In roomair, loss of vessels triggered abnormal angiogenesis that generatedpathogenic blood vessels on the top of the retina (marked in yellow inD). Treatment was applied during the return to room air by subcutaneousinjection. Lower graph: quantitation of healthy blood vessels,vaso-obliteration and pathogenic blood vessels between the control(n=10) and treated retinas (n=10). Treatment by PLXDC1-activatingcompound (A-Compound-1) highly suppressed pathogenic blood vessels (twoasterisks) while improving the amount of healthy blood vessels (oneasterisk). B. Representative images of flat-mounted control retinas(upper two images) and retinas from compound treated mice (lower twoimages). Red signal is blood vessel marker. C. The same retinas in Bwith vaso-obliteration areas marked in white color. These imagesillustrate that compound-treated retinas went through vaso-obliterationlike the control retinas. D. The same retinas in B with pathogenic bloodvessels marked in yellow color. These images illustrate thatcompound-treated retinas have highly decreased pathogenic blood vesselsas compared to the control retinas.

FIG. 8A-C show that PLXDC1-activating compound causes tumor shrinkage invivo. Treatment was done at day 0 by bolus IV injection. A. Raw data oftumor growth curves of the mice in the control group. B. Raw data oftumor growth curves of the mice in the treatment group. C. Comparison ofthe combined growth data of the control group and the treatment group.

FIG. 9 shows tumor morphological changes on live animals due to thetreatment by PLXDC1-activating compound. Pictures of the whole animalsin the experiment described in FIG. 11 show tumor morphological andcolor changes on day 1 and day 3. Treatment was done at day 0. Tumors inthe treatment groups becomes darker in color on day 1 due to thedestruction of tumor blood vessels and accumulation of blood in thetumors. Tumors in the treatment groups start to become yellower in coloron day 3, consistent with the onset of tumor necrosis due to the lack oftumor blood vessels.

FIG. 10A-B show tumor morphological changes on live animals due to thetreatment by PLXDC1-activating compound. Treatment was done at day 0.While the tumors in the control group have grown to large sizes, tumorsin the treatment groups have highly shrunk in size and become yellow incolor.

FIG. 11A-B show morphological changes of dissected tumors due to thetreatment by PLXDC1-activating compound. Pictures of the dissectedtumors in the experiment described in FIG. 11 show tumor morphologicaland color changes on day 7. While the tumors in the control group arereddish in color, tumors in the treatment groups have highly shrunk insize and become yellow in color, consistent with the lack of tumor bloodvessels and tumor necrosis.

DETAILED DESCRIPTION

The following description sets forth exemplary embodiments of thepresent technology. It should be recognized, however, that suchdescription is not intended as a limitation on the scope of the presentdisclosure but is instead provided as a description of exemplaryembodiments.

1. Definitions

As used in the present specification, the following words, phrases andsymbols are generally intended to have the meanings as set forth below,except to the extent that the context in which they are used indicatesotherwise.

A dash (“-”) that is not between two letters or symbols is used toindicate a point of attachment for a substituent. For example, —C(O)NH₂is attached through the carbon atom. A dash at the front or end of achemical group is a matter of convenience; chemical groups may bedepicted with or without one or more dashes without losing theirordinary meaning. A wavy line or a dashed line drawn through a line in astructure indicates a specified point of attachment of a group. Unlesschemically or structurally required, no directionality orstereochemistry is indicated or implied by the order in which a chemicalgroup is written or named.

The prefix “C_(u-v)” indicates that the following group has from u to vcarbon atoms. For example, “C₁₋₆ alkyl” indicates that the alkyl grouphas from 1 to 6 carbon atoms.

Reference to “about” a value or parameter herein includes (anddescribes) embodiments that are directed to that value or parameter perse. In certain embodiments, the term “about” includes the indicatedamount ±10%. In other embodiments, the term “about” includes theindicated amount ±5%. In certain other embodiments, the term “about”includes the indicated amount ±1%. Also, to the term “about X” includesdescription of “X”. Also, the singular forms “a” and “the” includeplural references unless the context clearly dictates otherwise. Thus,e.g., reference to “the compound” includes a plurality of such compoundsand reference to “the assay” includes reference to one or more assaysand equivalents thereof known to those skilled in the art.

“Alkyl” refers to an unbranched or branched saturated hydrocarbon chain.In some embodiments, alkyl has the indicated number of carbon atoms. Insome embodiments, alkyl has 1 to 40 carbon atoms (i.e., C₁₋₄₀ alkyl), 1to 30 carbon atoms (i.e., C₁₋₃₀ alkyl), 10 to 30 carbon atoms (i.e.,C₁₀₋₃₀ alkyl), 1 to 20 carbon atoms (i.e., C₁₋₂₀ alkyl), 1 to 12 carbonatoms (i.e., C₁₋₁₂ alkyl), 1 to 8 carbon atoms (i.e., C₁₋₈ alkyl), 1 to6 carbon atoms (i.e., C₁₋₆ alkyl) or 1 to 4 carbon atoms (i.e., C₁₋₄alkyl). Examples of alkyl groups include, e.g., methyl, ethyl, propyl,isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, 2-pentyl,isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl and 3-methylpentyl, octyl,nonyl, decyl, dodecyl, icosyl, docosyl, tetradecyl. When an alkylresidue having a specific number of carbons is named by chemical name oridentified by molecular formula, all positional isomers having thatnumber of carbons may be encompassed; thus, for example, “butyl”includes n-butyl (i.e., —(CH₂)₃CH₃), sec-butyl (i.e., —CH(CH₃)CH₂CH₃),isobutyl (i.e., —CH₂CH(CH₃)₂) and tert-butyl (i.e., —C(CH₃)₃); and“propyl” includes n-propyl (i.e., —(CH₂)₂CH₃) and isopropyl (i.e.,—CH(CH₃)₂).

Certain commonly used alternative chemical names may be used. Forexample, a divalent group such as a divalent “alkyl” group, a divalent“aryl” group, etc., may also be referred to as an “alkylene” group, an“arylene” group, respectively. Also, unless indicated explicitlyotherwise, where combinations of groups are referred to herein as onemoiety, e.g., arylalkyl or aralkyl, the last mentioned group containsthe atom by which the moiety is attached to the rest of the molecule.

“Alkenyl” refers to an alkyl group containing at least one carbon-carbondouble bond. In some embodiments, alkenyl has the indicated number ofcarbon atoms. In some embodiments, alkenyl has from 2 to 40 carbon atoms(i.e., C₂₋₄₀ alkenyl), 2 to 30 carbon atoms (i.e., C₂₋₃₀ alkenyl), 10 to30 carbon atoms (i.e., C₁₀₋₃₀ alkenyl), 2 to 20 carbon atoms (i.e.,C₂₋₂₀ alkenyl), 2 to 8 carbon atoms (i.e., C₂₋₈ alkenyl), 2 to 6 carbonatoms (i.e., C₂₋₆ alkenyl) or 2 to 4 carbon atoms (i.e., C₂₋₄ alkenyl).Examples of alkenyl groups include, e.g., ethenyl, propenyl, butadienyl(including 1,2-butadienyl and 1,3-butadienyl).

“Alkynyl” refers to an alkyl group containing at least one carbon-carbontriple bond. In some embodiments, alkynyl has the indicated number ofcarbon atoms. In some embodiments, alkynyl has from 2 to 40 carbon atoms(i.e., C₂₋₄₀ alkynyl), 2 to 30 carbon atoms (i.e., C₁₋₃₀ alkynyl), 10 to30 carbon atoms (i.e., C₁₀₋₃₀ alkynyl), 2 to 20 carbon atoms (i.e.,C₂₋₂₀ alkynyl), 2 to 8 carbon atoms (i.e., C₂₋₈ alkynyl), 2 to 6 carbonatoms (i.e., C₂₋₆ alkynyl) or 2 to 4 carbon atoms (i.e., C₂₋₄ alkynyl).The term “alkynyl” also includes those groups having one triple bond andone double bond.

“Alkoxy” refers to the group “alkyl-O—”. In some embodiments, alkoxy hasfrom 1 to 40 carbon atoms (i.e., —O—C₁₋₄₀ alkyl), 1 to 30 carbon atoms(i.e., —O—C₁₋₃₀ alkyl), 10 to 30 carbon atoms (i.e., —O—C₁₀₋₃₀ alkyl, 1to 20 carbon atoms (i.e., —O—C₁₋₂₀ alkyl), 1 to 12 carbon atoms (i.e.,—O—C₁₋₁₂ alkyl), 1 to 8 carbon atoms (i.e., —O—C₁₋₈alkyl), 1 to 6 carbonatoms (i.e., —O—C₁₋₆ alkyl) or 1 to 4 carbon atoms (i.e., —O—C₁₋₄alkyl). Examples of alkoxy groups include, e.g., methoxy, ethoxy,n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy,n-hexoxy and 1,2-dimethylbutoxy.

“Alkenoxy” refers to the group “alkene-O—”. In some embodiments,alkenoxy has from 2 to 40 carbon atoms (i.e., —O—C₂₋₄₀ alkene), 2 to 30carbon atoms (i.e., —O—C₂₋₃₀ alkene), 10 to 30 carbon atoms (i.e.,—O—C₁₀₋₃₀ alkene), 2 to 20 carbon atoms (i.e., —O—C₂₋₂₀ alkene), 2 to 12carbon atoms (i.e., —O—C₂₋₁₂ alkene), 2 to 8 carbon atoms (i.e., —O—C₂₋₈alkene), 2 to 6 carbon atoms (i.e., —O—C₂₋₆ alkene) or 2 to 4 carbonatoms (i.e., —O—C₂₋₄ alkene).

“Alkynoxy” refers to the group “alk2ne-O—”. In some embodiments,alkynoxy has from 1 to 40 carbon atoms (i.e., —O—C₂₋₄₀ alkyne), 2 to 30carbon atoms (i.e., —O—C₂₋₃₀ alkene), 10 to 30 carbon atoms (i.e.,—O—C₁₀₋₃₀ alkyne, 2 to 20 carbon atoms (i.e., —O—C₂₋₂₀ alkyne), 2 to 12carbon atoms (i.e., —O—C₂₋₁₂ alkyne), 2 to 8 carbon atoms (i.e., —O—C₂₋₈alkyne), 2 to 6 carbon atoms (i.e., —O—C₂₋₆ alkyne) or 2 to 4 carbonatoms (i.e., —O—C₂₋₄ alkyne).

The term “amido” as used herein refers to both —NR^(g)C(═O)R^(h) and—C(═O)NR^(g)R^(h), wherein each of R^(g) and R^(h) is independentlyhydrogen, alkyl, alkenyl, alkynyl, alkoxy, thioalkyl, aryl, aryl-alkyl,cycloalkyl, cycloalkyl-alkyl, haloalkyl, heterocyclyl,heterocyclyl-alkyl, heteroaryl, or heteroaryl-alkyl, and further whereineach R^(g) and R^(h) may be optionally substituted, as defined herein.

“Amino” refers to the group —NR^(y)R^(z) wherein R^(y) and R^(z) areindependently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclyl, aryl, heteroalkyl or heteroaryl; each of which may beoptionally substituted, as defined herein.

“Aryl” refers to an aromatic carbocyclic group having a single ring(e.g., monocyclic) or multiple rings (e.g., bicyclic or tricyclic)including fused systems. In some embodiments, aryl has 6 to 20 ringcarbon atoms (i.e., C₆₋₂₀ aryl), 6 to 12 ring carbon atoms (i.e., C₆₋₄₂aryl), or 6 to 10 ring carbon atoms (i.e., C₆₋₁₀ aryl). Examples of arylgroups include, e.g., phenyl, naphthyl, fluorenyl and anthryl. Aryl,however, does not encompass or overlap in any way with heteroaryldefined below. If one or more aryl groups are fused with a heteroaryl,the resulting ring system is heteroaryl. If one or more aryl groups arefused with a heterocyclyl, the resulting ring system is heterocyclyl.

“Arylalkyl” or “Aralkyl” refers to the group “aryl-alkyl-”.

“Carboxyl ester” or “ester” refer to both —OC(O)R^(x) and —C(O)OR^(x),wherein R^(x) is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl,aryl, heteroalkyl or heteroaryl; each of which may be optionallysubstituted, as defined herein.

“Carboxy” as used herein refers to —CO₂H, or a salt thereof. Exemplarycounter ions which can be used include, but are not limited to, Na⁺, K⁺,Li⁺, NH₄ ⁺ and others described herein.

“Cycloalkyl” refers to a saturated or partially unsaturated cyclic alkylgroup having a single ring or multiple rings including fused, bridgedand spiro ring systems. The term “cycloalkyl” includes cycloalkenylgroups (i.e., the cyclic group having at least one double bond) andcarbocyclic fused ring systems having at least one sp³ carbon atom(i.e., at least one non-aromatic ring). In some embodiments, cycloalkylhas from 3 to 20 ring carbon atoms (i.e., C₃₋₂₀ cycloalkyl), 3 to 12ring carbon atoms (i.e., C₃₋₁₂ cycloalkyl), 3 to 10 ring carbon atoms(i.e., C₃₋₄₀ cycloalkyl), 3 to 8 ring carbon atoms (i.e., C₃₋₈cycloalkyl), or 3 to 6 ring carbon atoms (i.e., C₃₋₆ cycloalkyl).Monocyclic groups include, for example, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Polycycliccycloalkyl refers to a cycloalkyl having at least two rings, which maybe a fused, bridged or spiro ring system. Polycyclic groups include, forexample, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl,norbornyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl and the like.“Spirocycloalkyl” refers to a polycyclic cycloalkyl group wherein atleast two rings are linked together by one common atom, for examplespiro[2.5]octanyl, spiro[4.5]decanyl, or spiro[5.5]undecanyl.Spirocycloalkyl may contain fused rings in the ring system, but notbridged rings. “Fused cycloalkyl” refers to a polycyclic cycloalkylgroup wherein at least two rings are linked together by two common atomswherein the two common atoms are connected through a covalent bond.Fused cycloalkyl does not contain any spiro or bridged rings in the ringsystem. “Bridged cycloalkyl” refers to a polycyclic cycloalkyl thatcontains a bridge—an alkylene (such as C₁₋₄ alkylene) group that connecttwo “bridgehead” atoms. Non-limiting examples of bridged cycloalkylinclude bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl,norbornyl, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Bridged cycloalkylmay contain fused and/or spiro rings in the ring system. Further, theterm cycloalkyl is intended to encompass any non-aromatic ring which maybe fused to an aryl ring, regardless of the attachment to the remainderof the molecule.

“Halogen” or “halo” refers to atoms occupying group VIIA of the periodictable, such as fluoro, chloro, bromo or iodo.

“Haloalkyl” refers to an unbranched or branched alkyl group as definedabove, wherein one or more (e.g., 1 to 6, 1 to 5 or 1 to 3) hydrogenatoms are replaced by a halogen. For example, where a residue issubstituted with more than one halogen, it may be referred to by using aprefix corresponding to the number of halogen moieties attached.Dihaloalkyl and trihaloalkyl refer to alkyl substituted with two (“di”)or three (“tri”) halo groups, which may be, but are not necessarily, thesame halogen. Examples of haloalkyl include, e.g., trifluoromethyl,difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl,1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl and thelike.

“Haloalkoxy” refers to an alkoxy group as defined above, wherein one ormore (e.g., 1 to 6, 1 to 5 or 1 to 3) hydrogen atoms are replaced by ahalogen.

“Hydroxyalkyl” refers to an alkyl group as defined above, wherein one ormore (e.g., 1 to 6, 1 to 5 or 1 to 3) hydrogen atoms are replaced by ahydroxy group. A non-limiting example of hydroxyalkyl is —(CH₂)₁₋₄—OH.

“Heteroalkyl” refers to an alkyl group in which one or more, but not allof the carbon atoms (and any associated hydrogen atoms) are eachindependently replaced with the same or different heteroatomic group,provided the point of attachment to the remainder of the molecule isthrough a carbon atom. The term “heteroalkyl” includes unbranched orbranched saturated chain having carbon and heteroatoms. By way ofexample, 1, 2 or 3 carbon atoms may be independently replaced with thesame or different heteroatomic group. Heteroatomic groups include, butare not limited to, —NR^(y)—, —O—, —S—, —S(O)—, —S(O)₂—, and the like,wherein R^(y) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclyl, aryl, heteroalkyl or heteroaryl; each of which may beoptionally substituted, as defined herein. Examples of heteroalkylgroups include, e.g., ethers (e.g., —CH₂OCH₃, —CH(CH₃)OCH₃, —CH₂CH₂OCH₃,—CH₂CH₂OCH₂CH₂OCH₃, etc.), thioethers (e.g., —CH₂SCH₃, —CH(CH₃)SCH₃,—CH₂CH₂SCH₃, —CH₂CH₂SCH₂CH₂SCH₃, etc.), sulfones (e.g., —CH₂S(O)₂CH₃,—CH(CH₃)S(O)₂CH₃, —CH₂CH₂S(O)₂CH₃, —CH₂CH₂S(O)₂CH₂CH₂OCH₃, etc.) andamines (e.g., —CH₂NR^(y)CH₃, —CH(CH₃)NR^(y)CH₃, —CH₂CH₂NR^(y)CH₃,—CH₂CH₂NR^(y)CH₂CH₂NR^(y)CH₃, etc., where R^(y) is hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroalkyl, orheteroaryl; each of which may be optionally substituted, as definedherein). In some embodiments, heteroalkyl includes 1 to 10 carbon atoms(C₁₋₁₀ heteroalkyl), 1 to 8 carbon atoms (C₁₋₈ heteroalkyl), or 1 to 4carbon atoms (C₁₋₄ heteroalkyl); and 1 to 3 heteroatoms, 1 to 2heteroatoms, or 1 heteroatom.

“Heteroaryl” refers to an aromatic group having a single ring, multiplerings or multiple fused rings, with one or more ring heteroatomsindependently selected from nitrogen, oxygen, and sulfur. As usedherein, heteroaryl includes 1 to 20 ring carbon atoms (i.e., C₁₋₂₀heteroaryl), 3 to 12 ring carbon atoms (i.e., C₃₋₁₂ heteroaryl), or 3 to8 carbon ring atoms (i.e., C₃₋₈ heteroaryl), and 1 to 5 ringheteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2ring heteroatoms, or 1 ring heteroatom independently selected fromnitrogen, oxygen and sulfur. In certain instances, heteroaryl includes5-10 membered ring systems, 5-7 membered ring systems, or 5-6 memberedring systems, each independently having 1 to 4 ring heteroatoms, 1 to 3ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatomindependently selected from nitrogen, oxygen and sulfur. Examples ofheteroaryl groups include, e.g., acridinyl, benzimidazolyl,benzothiazolyl, benzindolyl, benzofuranyl, benzothiazolyl,benzothiadiazolyl, benzonaphthofuranyl, benzoxazolyl, benzothienyl(benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridyl,carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl,isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl,isoquinolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl,1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl,1-oxidopyridazinyl, phenazinyl, phthalazinyl, pteridinyl, purinyl,pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl,quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl,thiazolyl, thiadiazolyl, triazolyl, tetrazolyl and triazinyl. Examplesof the fused-heteroaryl rings include, but are not limited to,benzo[d]thiazolyl, quinolinyl, isoquinolinyl, benzo[b]thiophenyl,indazolyl, benzo[d]imidazolyl, pyrazolo[1,5-a]pyridinyl andimidazo[1,5-a]pyridinyl, where the heteroaryl can be bound via eitherring of the fused system. Any aromatic ring, having a single or multiplefused rings, containing at least one heteroatom, is considered aheteroaryl regardless of the attachment to the remainder of the molecule(i.e., through any one of the fused rings). Heteroaryl does notencompass or overlap with aryl as defined above.

“Heterocyclyl” refers to a saturated or partially unsaturated cyclicalkyl group, with one or more ring heteroatoms independently selectedfrom nitrogen, oxygen and sulfur. The term “heterocyclyl” includesheterocycloalkenyl groups (i.e., the heterocyclyl group having at leastone double bond), bridged-heterocyclyl groups, fused-heterocyclyl groupsand spiro-heterocyclyl groups. A heterocyclyl may be a single ring ormultiple rings wherein the multiple rings may be fused, bridged orspiro, and may comprise one or more (e.g., 1 to 3) oxo (═O) or N-oxide(—O⁻) moieties. Any non-aromatic ring containing at least one heteroatomis considered a heterocyclyl, regardless of the attachment (i.e., can bebound through a carbon atom or a heteroatom). Further, the termheterocyclyl is intended to encompass any non-aromatic ring containingat least one heteroatom, which ring may be fused to an aryl orheteroaryl ring, regardless of the attachment to the remainder of themolecule. As used herein, heterocyclyl has 2 to 20 ring carbon atoms(i.e., C₂₋₂₀ heterocyclyl), 2 to 12 ring carbon atoms (i.e., C₂₋₁₂heterocyclyl), 2 to 10 ring carbon atoms (i.e., C₂₋₁₀ heterocyclyl), 2to 8 ring carbon atoms (i.e., C₂₋₈ heterocyclyl), 3 to 12 ring carbonatoms (i.e., C₃₋₁₂ heterocyclyl), 3 to 8 ring carbon atoms (i.e., C₃₋₈heterocyclyl), or 3 to 6 ring carbon atoms (i.e., C₃₋₆ heterocyclyl);having 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ringheteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independentlyselected from nitrogen, sulfur or oxygen. In certain instances,heterocyclyl includes 3- to 10-membered heterocyclyl having 3-10 totalring atoms, 5- to 7-membered heterocyclyl having 5-7 total ring atoms,or 5- or 6-membered heterocyclyl having 5 or 6 total ring atoms.Examples of heterocyclyl groups include, e.g., azetidinyl, azepinyl,benzodioxolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzopyranyl,benzodioxinyl, benzopyranonyl, benzofuranonyl, dioxolanyl,dihydropyranyl, hydropyranyl, thienyl[1,3]dithianyl,decahydroisoquinolyl, furanonyl, imidazolinyl, imidazolidinyl,indolinyl, indolizinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl,morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl,2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, oxiranyl, oxetanyl,phenothiazinyl, phenoxazinyl, piperidinyl, piperazinyl, 4-piperidonyl,pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl,tetrahydrofuryl, tetrahydropyranyl, trithianyl, tetrahydroquinolinyl,thiophenyl (i.e., thienyl), tetrahydropyranyl, thiomorpholinyl,thiamorpholinyl, 1-oxo-thiomorpholinyl and 1,1-dioxo-thiomorpholinyl.The term “heterocyclyl” also includes “spiroheterocyclyl” when there areat least two rings are linked together by one common atom. Examples ofthe spiro-heterocyclyl rings include, e.g., bicyclic and tricyclic ringsystems, such as 2-oxa-7-azaspiro[3.5]nonanyl,2-oxa-6-azaspiro[3.4]octanyl and 6-oxa-1-azaspiro[3.3]heptanyl. Examplesof the fused-heterocyclyl rings include, but are not limited to,1,2,3,4-tetrahydroisoquinolinyl,4,5,6,7-tetrahydrothieno[2,3-c]pyridinyl, indolinyl and isoindolinyl,where the heterocyclyl can be bound via either ring of the fused system.Examples of heterocyclyl include sugar moieties such as glucose,mannose, allose, altrose, gulose, idose, galactose, and talose.

The terms “alkylthio” or “thioalkyl” as used herein refer to —S-alkyl,where the term alkyl is as defined herein.

The term “sulfonamido” as used herein refer to both —NR^(g)S(═O)₂R^(h)and —S(═O)₂NR^(g)R^(h), wherein each of R^(g) and R^(h) is independentlyhydrogen, alkyl, alkenyl, alkynyl, alkoxy, thioalkyl, aryl, aryl-alkyl,cycloalkyl, cycloalkyl-alkyl, haloalkyl, heterocyclyl,heterocyclyl-alkyl, heteroaryl, or heteroaryl-alkyl, and further whereineach R^(g) and R^(h) may be optionally substituted, as defined herein.

The term “sulfinamido” as used herein refer to both —NR^(g)S(═O)R^(h)and —S(═O)NR^(g)R^(h), wherein each of R^(g) and R^(h) is independentlyhydrogen, alkyl, alkenyl, alkynyl, alkoxy, thioalkyl, aryl, aryl-alkyl,cycloalkyl, cycloalkyl-alkyl, haloalkyl, heterocyclyl,heterocyclyl-alkyl, heteroaryl, or heteroaryl-alkyl, and further whereineach R^(g) and R^(h) may be optionally substituted, as defined herein.

The term “sulfoxide” or “sulfoxido” refers to the group —S(═O)—R^(g),wherein R^(g) is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, thioalkyl,aryl, aryl-alkyl, cycloalkyl, cycloalkyl-alkyl, haloalkyl, heterocyclyl,heterocyclyl-alkyl, heteroaryl, or heteroaryl-alkyl, and further whereinR^(g) may be optionally substituted, as defined herein.

The term “sulfonyl” refers to the group —S(O)₂—R^(g), wherein R^(g) ishydrogen, alkyl, alkenyl, alkynyl, alkoxy, thioalkyl, aryl, aryl-alkyl,cycloalkyl, cycloalkyl-alkyl, haloalkyl, heterocyclyl,heterocyclyl-alkyl, heteroaryl, or heteroaryl-alkyl, and further whereinR^(g) may be optionally substituted, as defined herein. “Sugar moiety”refers to a monovalent radical of a sugar molecule, such as amonosaccharide molecule, including glucose (also known as dextrose),fructose, galactose, mannose, allose, altrose, gulose, idose, andtalose. As used herein, a sugar moiety a heterocyclyl substituted withOH and/or hydoxyalkyl groups. However, it is understood that a sugarmoiety can exist in a liner form as an alkyl substituted with oxo and OHgroups.

The terms “optional” or “optionally” means that the subsequentlydescribed event or circumstance may or may not occur and that thedescription includes instances where said event or circumstance occursand instances in which it does not. Also, the term “optionallysubstituted” refers to any one or more (e.g., 1 to 5 or 1 to 3) hydrogenatoms on the designated atom or group may or may not be replaced by amoiety other than hydrogen.

In certain embodiments, “substituted” includes any of the above alkyl,heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl orheteroaryl groups in which one or more (e.g., 1 to 5 or 1 to 3) hydrogenatoms are independently replaced with halo, cyano, nitro, azido, oxo,alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocyclyl, aryl,heteroaryl, —NR^(g)R^(h), —C(NR^(g))R^(h), —C(NR^(g))(NR^(h) ₂),—NR^(g)C(═O)R^(h), —NR^(g)C(═O)NR^(g)R^(h), —NR^(g)C(═O)OR^(h),—NR^(g)S(═O)₁₋₂R^(h), —C(═O)R^(g), —C(═O)OR^(g), —OC(═O)OR^(g),—OC(═O)R^(g), —C(═O)NR^(g)R^(h), —OC(═O)NR^(g)R^(h), —OR^(g), —SR^(g),—S(═O)R^(g), —S(═O)₂R^(g), —OS(═O)₁₋₂R^(g), —S(═O)₁₋₂OR^(g),—NR^(g)S(═O)₁₋₂NR^(g)R^(h), ═NSO₂R^(g), ═NOR^(g), —S(═O)₁₋₂NR^(g)R^(h),—CR^(g)(═NOH), —NR^(g)C(═NR^(h))(NR^(h)R^(h)), —SF₅, —SCF₃ or —OCF₃. Incertain embodiments, “substituted” also means any of the above groups inwhich one or more (e.g., 1 to 5 or 1 to 3) hydrogen atoms are replacedwith —C(═O)R^(g), —C(═O)OR^(g), —C(═O)NR^(g)R^(h), —CH₂SO₂R^(g), or—CH₂SO₂NR^(g)R^(h). In the foregoing, each of R^(g) and R^(h) isindependently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, thioalkyl,aryl, aralkyl, cycloalkyl, cycloalkyl-alkyl, haloalkyl, heterocyclyl,heterocyclyl-alkyl, heteroaryl, and/or heteroaryl-alkyl. In certainembodiments, “substituted” also means any of the above groups in whichone or more (e.g., 1 to 5 or 1 to 3) hydrogen atoms are replaced withhalo, hydroxy, alkyl, alkylhydroxy, or oxo groups.

Polymers or similar indefinite structures arrived at by definingsubstituents with further substituents appended ad infinitum (e.g., asubstituted aryl having a substituted alkyl which is itself substitutedwith a substituted aryl group, which is further substituted by asubstituted heteroalkyl group, etc.) are not intended for inclusionherein. Unless otherwise noted, the maximum number of serialsubstitutions in compounds described herein is three. For example,serial substitutions of substituted aryl groups with two othersubstituted aryl groups are limited to ((substituted aryl)substitutedaryl)substituted aryl. Similarly, the above definitions are not intendedto include impermissible substitution patterns (e.g., methyl substitutedwith 5 fluorines or heteroaryl groups having two adjacent oxygen ringatoms). Such impermissible substitution patterns are well known to theskilled artisan.

In certain embodiments, as used herein, the phrase “one or more” refersto one to five. In certain embodiments, as used herein, the phrase “oneor more” refers to one to three.

Any compound or structure given herein, is also intended to representunlabeled forms as well as isotopically labeled forms of the compounds.These forms of compounds may also be referred to as “isotopicallyenriched analogs.” Isotopically labeled compounds have structuresdepicted herein, except that one or more atoms are replaced by an atomhaving a selected atomic mass or mass number. Examples of isotopes thatcan be incorporated into the disclosed compounds include isotopes ofhydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine andiodine, such as ²H, ³H, ¹¹C, ¹³C, ¹⁴C, ¹³N, ¹⁵N, ¹⁵O, ¹⁷O, ¹⁸O, ³¹P,³²P, ³⁵S, ¹⁸F, ³⁶Cl, ¹²³I, and ¹²⁵I, respectively. Various isotopicallylabeled compounds of the present disclosure, for example those intowhich radioactive isotopes such as ³H and ¹⁴C are incorporated. Suchisotopically labelled compounds may be useful in metabolic studies,reaction kinetic studies, detection or imaging techniques, such aspositron emission tomography (PET) or single-photon emission computedtomography (SPECT) including drug or substrate tissue distributionassays or in radioactive treatment of subjects.

The term “isotopically enriched analogs” includes “deuterated analogs”of compounds described herein in which one or more hydrogens is/arereplaced by deuterium, such as a hydrogen on a carbon atom. Suchcompounds may exhibit increased resistance to metabolism and are thususeful for increasing the half-life of any compound when administered toa mammal, particularly a human. See, for example, Foster, “DeuteriumIsotope Effects in Studies of Drug Metabolism,” Trends Pharmacol. Sci.5(12):524-527 (1984). Such compounds are synthesized by means well knownin the art, for example by employing starting materials in which one ormore hydrogens have been replaced by deuterium.

Deuterium labelled or substituted therapeutic compounds of thedisclosure may have improved DMPK (drug metabolism and pharmacokinetics)properties, relating to distribution, metabolism and excretion (ADME).Substitution with heavier isotopes such as deuterium may afford certaintherapeutic advantages resulting from greater metabolic stability, forexample increased in vivo half-life, reduced dosage requirements and/oran improvement in therapeutic index. An ¹⁸F, ³H, ¹¹C labeled compoundmay be useful for PET or SPECT or other imaging studies. Isotopicallylabeled compounds of this disclosure can generally be prepared bycarrying out the procedures disclosed in the schemes or in the examplesand preparations described below by substituting a readily availableisotopically labeled reagent for a non-isotopically labeled reagent.

The concentration of such a heavier isotope, specifically deuterium, maybe defined by an isotopic enrichment factor. In the compounds of thisdisclosure any atom not specifically designated as a particular isotopeis meant to represent any stable isotope of that atom. Unless otherwisestated, when an atom is represented by its name or letter symbol, suchas, H, C, O, or N, it is understood that the atom has its naturalabundance isotopic composition. For example, when a position isdesignated specifically as “H” or “hydrogen”, the position is understoodto have hydrogen at its natural abundance isotopic composition.Accordingly, in the compounds of this disclosure any atom specificallydesignated as a deuterium (D) is meant to represent deuterium.

In many cases, the compounds of this disclosure are capable of formingacid and/or base salts by virtue of the presence of amino and/orcarboxyl groups or groups similar thereto.

Provided also are a pharmaceutically acceptable salt, isotopicallyenriched analog, deuterated analog, stereoisomer, and mixture ofstereoisomers of the compounds described herein. “Pharmaceuticallyacceptable” or “physiologically acceptable” refer to compounds, salts,compositions, dosage forms and other materials which are useful inpreparing a pharmaceutical composition that is suitable for veterinaryor human pharmaceutical use.

The term “pharmaceutically acceptable salt” of a given compound refersto salts that retain the biological effectiveness and properties of thegiven compound and which are not biologically or otherwise undesirable.“Pharmaceutically acceptable salts” or “physiologically acceptablesalts” include, for example, salts with inorganic acids and salts withan organic acid. In addition, if the compounds described herein areobtained as an acid addition salt, the free base can be obtained bybasifying a solution of the acid salt. Conversely, if the product is afree base, an addition salt, particularly a pharmaceutically acceptableaddition salt, may be produced by dissolving the free base in a suitableorganic solvent and treating the solution with an acid, in accordancewith conventional procedures for preparing acid addition salts from basecompounds. Those skilled in the art will recognize various syntheticmethodologies that may be used to prepare nontoxic pharmaceuticallyacceptable addition salts. Pharmaceutically acceptable acid additionsalts may be prepared from inorganic and organic acids. Salts derivedfrom inorganic acids include, e.g., hydrochloric acid, hydrobromic acid,sulfuric acid, nitric acid, phosphoric acid and the like. Salts derivedfrom organic acids include, e.g., acetic acid, propionic acid, gluconicacid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonicacid, succinic acid, maleic acid, fumaric acid, tartaric acid, citricacid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid,ethanesulfonic acid, p-toluene-sulfonic acid, salicylic acid and thelike. Salts derived from organic acids may be derived from anhydrousorganic acids or hydrates thereof. Likewise, pharmaceutically acceptablebase addition salts can be prepared from inorganic and organic bases.Salts derived from inorganic bases include, by way of example only,sodium, potassium, lithium, aluminum, ammonium, calcium and magnesiumsalts. Salts derived from organic bases include, but are not limited to,salts of primary, secondary and tertiary amines, such as alkyl amines(i.e., NH₂(alkyl)), dialkyl amines (i.e., HN(alkyl)₂), trialkyl amines(i.e., N(alkyl)₃), substituted alkyl amines (i.e., NH₂(substitutedalkyl)), di(substituted alkyl) amines (i.e., HN(substituted alkyl)₂),tri(substituted alkyl) amines (i.e., N(substituted alkyl)₃), alkenylamines (i.e., NH₂(alkenyl)), dialkenyl amines (i.e., HN(alkenyl)₂),trialkenyl amines (i.e., N(alkenyl)₃), substituted alkenyl amines (i.e.,NH₂(substituted alkenyl)), di(substituted alkenyl) amines (i.e.,HN(substituted alkenyl)₂), tri(substituted alkenyl) amines (i.e.,N(substituted alkenyl)₃, mono-, di- or tri-cycloalkyl amines (i.e.,NH₂(cycloalkyl), HN(cycloalkyl)₂, N(cycloalkyl)₃), mono-, di- ortri-arylamines (i.e., NH₂(aryl), HN(aryl)₂, N(aryl)₃) or mixed amines,etc. Specific examples of suitable amines include, by way of exampleonly, isopropylamine, trimethyl amine, diethyl amine, tri(iso-propyl)amine, tri(n-propyl) amine, ethanolamine, 2-dimethylaminoethanol,piperazine, piperidine, morpholine, N-ethylpiperidine, and the like.

Some of the compounds exist as tautomers. Tautomers are in equilibriumwith one another. For example, amide containing compounds may exist inequilibrium with imidic acid tautomers. Regardless of which tautomer isshown and regardless of the nature of the equilibrium among tautomers,the compounds are understood by one of ordinary skill in the art tocomprise tautomers. Thus, the amide containing compounds are understoodto include their imidic acid tautomers. Likewise, the imidic acidcontaining compounds are understood to include their amide tautomers.

A “stereoisomer” refers to a compound made up of the same atoms bondedby the same bonds but having different three-dimensional structures,which are not interchangeable. The present invention contemplatesvarious stereoisomers and mixtures thereof and includes “

Stereoisomers include enantiomers, diastereomers, and otherstereoisomeric forms that may be defined, in terms of absolutestereochemistry, as (R)- or (S)- or, as (D)- or (L)-for amino acids. Thepresent invention is meant to include all such possible isomers, as wellas their racemic and optically pure forms. Optically active (+) and (−),(R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiralsynthons or chiral reagents, or resolved using conventional techniques,for example, chromatography and fractional crystallization. Conventionaltechniques for the preparation/isolation of individual enantiomersinclude chiral synthesis from a suitable optically pure precursor orresolution of the racemate (or the racemate of a salt or derivative)using, for example, chiral high pressure liquid chromatography (HPLC).Stereoisomers also include geometric isomers when the compoundsdescribed herein contain olefinic double bonds or other centers ofgeometric asymmetry. Unless specified otherwise, it is intended thatsuch compounds include both E and Z geometric isomers.

“Enantiomers” are two stereoisomers whose molecules arenon-superimposable mirror images of one another. “Diastereomers” arestereoisomers that have at least two asymmetric atoms, but which are notmirror-images of each other.

Relative centers of the compounds as depicted herein are indicatedgraphically using the “thick bond” style and absolute stereochemistry isdepicted using wedge bonds.

When the stereochemistry of a disclosed compound is named or depicted bystructure, the named or depicted stereoisomer is at least 60%, 70%, 80%,90%, 99% or 99.9% by weight pure relative to the other stereoisomers.When a single enantiomer is named or depicted by structure, the depictedor named enantiomer is at least 60%, 70%, 80%, 90%, 99% or 99.9% byweight optically pure. Percent optical purity by weight is the ratio ofthe weight of the enantiomer over the weight of the enantiomer plus theweight of its optical isomer.

When the geometry of a disclosed compound is named or depicted bystructure, the named or depicted geometrical isomer is at least 60%,70%, 80%, 90%, 99% or 99.9% by weight pure relative to the othergeometrical isomers.

In certain embodiments, where one or more stereocenters are present, acompound disclosed herein may be provided as a racemic mixture. Incertain embodiments, where one or more stereocenters are present, acompound disclosed herein may be provided as a single enantiomer. Forexample, a compound may be provided in a composition having greater thanabout 30% ee, about 40% ee, about 50% ee, about 60% ee, about 70% ee,about 80% ee, about 90% ee, about 95% ee, about 97% ee, about 98% ee,about 99% ee, or greater. In certain such embodiments, compounds may beprovided in a diastereomerically enriched composition. For example, adiastereomerically enriched composition comprising a compound disclosedherein may have greater than about 30% de, about 40% de, about 50% de,about 60% de, about 70% de, about 80% de, about 90% de, about 95% de,about 97% de, about 98% de, about 99% de, or greater.

In certain embodiments, the therapeutic preparation may be enriched toprovide predominantly one enantiomer of a compound (e.g., of Formula(I)). An enantiomerically enriched mixture may comprise, for example, atleast about 60 mol percent of one enantiomer, or more preferably atleast about 75, about 90, about 95, or even about 99 mol percent. Incertain embodiments, the compound enriched in one enantiomer issubstantially free of the other enantiomer, wherein substantially freemeans that the substance in question makes up less than about 10%, orless than about 5%, or less than about 4%, or less than about 3%, orless than about 2%, or less than about 1% as compared to the amount ofthe other enantiomer, e.g., in the composition or compound mixture. Forexample, if a composition or compound mixture contains about 98 grams ofa first enantiomer and about 2 grams of a second enantiomer, it would besaid to contain about 98 mol percent of the first enantiomer and onlyabout 2% of the second enantiomer.

In certain embodiments, the therapeutic preparation may be enriched toprovide predominantly one diastereomer of a compound (e.g., of Formula(I)). A diastereomerically enriched mixture may comprise, for example,at least about 60 mol percent of one diastereomer, or more preferably atleast about 75, about 90, about 95, or even about 99 mol percent.

The term “subject” to which administration is contemplated includes, butis not limited to, humans (i.e., a male or female of any age group,e.g., a pediatric subject (e.g., infant, child, adolescent) or adultsubject (e.g., young adult, middle-aged adult or senior adult)) and/orother primates (e.g., cynomolgus monkeys, rhesus monkeys); mammals,including commercially relevant mammals such as cattle, pigs, horses,sheep, goats, cats, and/or dogs; and/or birds, including commerciallyrelevant birds such as chickens, ducks, geese, quail, and/or turkeys. Inone embodiment, the subject is human.

As used herein, a therapeutic that “prevents” a disorder or conditionrefers to a compound that, in a statistical sample, reduces theoccurrence of the disorder or condition in the treated sample relativeto an untreated control sample, or delays the onset or reduces theseverity of one or more symptoms of the disorder or condition relativeto the untreated control sample.

The term “treating” means to decrease, suppress, attenuate, diminish,arrest, or stabilize the development or progression of a disease (e.g.,a disease or disorder delineated herein), lessen the severity of thedisease or improve the symptoms associated with the disease. Treatmentincludes treating a symptom of a disease, disorder or condition. If itis administered prior to clinical manifestation of the unwantedcondition (e.g., disease or other unwanted state of the subject) thenthe treatment is prophylactic (i.e., it protects the subject againstdeveloping the unwanted condition), whereas if it is administered aftermanifestation of the unwanted condition, the treatment is therapeutic,(i.e., it is intended to diminish, ameliorate, or stabilize the existingunwanted condition or side effects thereof).

“Pathogenic blood vessels” are blood vessels that are not involved inthe vascularization of normal organs but, instead, are involved invascularization of diseased tissues, such as the new blood vessels thatdrive vision diseases or the new blood vessels in tumors that tumorsdepend on to survive. “Pathogenic blood vessel,” in some embodiments,refers to an existing blood vessel that may have vascularized a diseasedtissue, for instance, a tumor. In other embodiments, a pathogenic bloodvessel may be a blood vessel that is a newly formed blood vesselinvolved in disease onset and/or progression of, for example, cancer,diabetic retinopathy, age-related macular degeneration (AMD),retinopathy of prematurity and/or any other diseases having etiologiesassociated with angiogeneis.

Abbreviations

-   -   DCM dichloromethane    -   DIPEA diisopropylethylamine    -   DMA dimethylacetamide    -   DMAP dimethylaminopyridine    -   DMF dimethylformamide    -   DMSO dimethyl sulfoxide    -   EDCI 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide    -   Equiv or eq equivalent    -   ESI electrospray ionization    -   EtOAc ethyl acetate    -   EtOH ethanol    -   EtONa sodium ethoxide    -   HOAc or AcOH acetic acid    -   HOBt 1-hydroxybenzotriazole    -   HPLC high performance liquid chromatography    -   HRMS high-resolution mass spectrometry    -   LC liquid chromatography    -   LCMS liquid chromatography-mass spectrometry    -   mCPBA meta-chloroperoxybenzoic acid    -   MeOH methanol    -   NMM N-methylmorpholine    -   NMP N-methyl-2-pyrrolidone    -   OXONE® Potassium peroxymonosulfate    -   mPEG methoxypoly(ethylene glycol)    -   rt room temperature    -   TEA triethylamine    -   THF tetrahydrofuran    -   TLC thin-layer chromatography    -   TsOH p-toluenesulfonic acid    -   PPSE Trimethylsilyl polyphosphate

2. Compounds

In certain embodiments, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   n is 0, 1, 2, 3 or 4;    -   R¹ is selected from optionally substituted amino, optionally        substituted aryl, optionally substituted cycloalklyl, optionally        substituted heterocyclyl, and optionally substituted heteroaryl;    -   R² is selected from H, halo, alkyl, alkenyl, alkynyl, —OH,        alkoxy, —CN, —NO₂, alkylthio, sulfoxido, sulfonyl, and amino;    -   R⁵, R⁷ and R⁸ are each independently selected from H, halo,        alkyl, alkenyl, alkynyl, hydroxy, alkoxy, alkenoxy, alkynoxy,        alkylthio, sulfoxido, sulfonyl, carboxy, ester, —CN, —NO₂,        amino, and amido;    -   R⁶ is selected from H, halo, alkyl, hydroxy, alkoxy, alkylthio,        sulfoxido, sulfonyl, carboxy, ester, —CN, —NO₂, amino, amido,        sulfinamido, sulfonamido, optionally substituted heterocyclyl,        optionally substituted heteroaryl, poly(ethylene glycol), and        methoxypoly(ethylene glycol), or    -   R⁶ and IV together with atoms to which they are attached form an        optionally substituted cycloalkyl, optionally substituted        heterocyclyl, optionally substituted aryl, or optionally        substituted heteroaryl; and    -   each R⁹ is independently selected from halo, alkyl, —OH, alkoxy,        —CN, and amino.

In certain embodiments, when R² is C₁₋₆ alkyl, R⁶ is not C₁₋₆ alkyl orC₁₋₆ alkoxy. In other embodiments, when R² is C₁₋₃ alkyl, R⁶ is not C₁₋₃alkyl or C₁₋₃ alkoxy. In certain embodiments, when R² is ethyl, then R⁶is not methyl or methoxy.

In certain embodiments, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   n is 0, 1, 2, 3 or 4;    -   R¹ is selected from optionally substituted amino, optionally        substituted aryl, optionally substituted cycloalkyl, optionally        substituted heterocyclyl, and optionally substituted heteroaryl;    -   R² is selected from halo, alkyl, alkenyl, alkynyl, alkoxy,        alkenoxy, alkynoxy, —CN, and —NO₂;    -   R⁵, R⁷ and R⁸ are each independently selected from H, halo,        alkyl, alkenyl, hydroxy, and alkoxy;    -   R⁶ is selected from halo, alkyl, alkenyl, alkynyl hydroxy,        alkoxy, alkylthio, sulfoxide, sulfonyl, carboxy, ester, —NO₂—CN,        amino, and amido; and    -   each R⁹ is independently selected from halo, hydroxy, and        alkoxy.

In certain embodiments of Formula (I):

-   -   n is 0 or 1;    -   R¹ is selected from optionally substituted amino, optionally        substituted heterocyclyl, and optionally substituted heteroaryl;    -   R² is selected from alkyl, alkoxy, alkenoxy, alkynoxy, —CN, and        —NO₂;    -   R⁵, R⁷ and R⁸ are each independently selected from H and alkoxy;    -   R⁶ is selected from halo, alkyl, alkoxy, sulfoxido, sulfonyl,        carboxy, ester, —NO₂ and amido; and    -   each R⁹ is independently halo or alkoxy.

In certain embodiments, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   n is 0 or 1;    -   R¹ is selected from amino, optionally substituted amino        heterocyclyl, and optionally substituted amino heteroaryl;    -   R² is selected from alkyl, alkoxy, —CN, and —NO₂;    -   R⁵, R⁷ and R⁸ are each independently selected from H and alkoxy;    -   R⁶ is selected from halo, alkyl, alkoxy, sulfoxido, sulfonyl,        carboxy, ester, —NO₂ and amido; and each R⁹ is independently        halo or alkoxy.

In certain embodiments, the compound of Formula (I) described above hasat least one of the following:

1) R² is selected from C₂₋₃₀alkyl, —OH, C₁₋₄₀alkoxy, C₁₋₄₀alkenoxy,C₁₋₄₀alkynoxy, —NO₂, alkylthio, sulfoxido, sulfonyl, and amino, where

a) when R² is ethyl, then R⁶ is not methyl or methoxy, and/or

b) when R² is methoxy, then R⁶ is not halo, C₁₋₂ alkyl or C₁₋₂ alkoxy;

2) R¹ is optionally substituted amino heteroaryl, optionally substitutedamino bridged heterocyclyl, optionally substituted amino fusedheterocyclyl, or optionally substituted amino cycloheptyl;

3) R¹ is heterocyclyl optionally substituted with one halo, amino,hydroxy, alkoxy, —CN, —NO₂, alkyl, carboxy, alkylthio, sulfoxido,sulfonyl, sulfinamido, sulfonamido, optionally substituted cycloalkyl,optionally substituted heterocyclyl, optionally substituted heteroaryl,poly(ethylene glycol), or methoxypoly(ethylene glycol),

where if the substituent is alkyl, the alkyl is further substituted withone substituent selected from halo, amino, alkoxy, —CN, —NO₂, carboxy,ester, alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido,cycloalkyl, heterocyclyl, poly(ethylene glycol), methoxypoly(ethyleneglycol), pyrrolidinyl and piperidinyl; or the alkyl is substituted withat least one —OR³¹, wherein R³¹ is poly(ethylene glycol) ormethoxypoly(ethylene glycol);

4) R¹ is amino substituted with at least one substituent selected fromalkyl, cycloalkyl, heterocyclyl, heteroaryl, poly(ethylene glycol) ormethoxypoly(ethylene glycol) and amino,

where the alkyl is substituted with at least one substituent selectedfrom halo, amino, hydroxy, alkoxy, —CN, —NO₂, amido, carboxy, ester,alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido, cycloalkyl,heterocyclyl, and heteroaryl; or

5) R⁶ is alkyl substituted with at least one substituent selected fromhalo, amino, hydroxy, alkoxy, cycloalkoxy, heterocycloalkoxy, aryloxy,heteroaryloxy, poly(ethylene glycol)-oxy, methoxypoly(ethyleneglycol)-oxy, —CN, —NO₂, oxo, amido, carboxy, ester, alkylthio,sulfoxido, sulfonyl, sulfinamido, sulfonamido, heterocyclyl, cycloalkyl,aryl, heteroaryl, poly(ethylene glycol) and methoxypoly(ethyleneglycol).

In certain embodiments, provided is a compound of Formula (I′):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   n is 0, 1, 2, 3 or 4;    -   R¹ is selected from amino, heterocyclyl, and heteroaryl;    -   R² is selected from H, halo, alkyl, alkenyl, alkynyl, —OH,        alkoxy, —CN, —NO₂, alkylthio, sulfoxido, sulfonyl, and amino;    -   R⁵, R⁷ and R⁸ are each independently selected from H, halo,        alkyl, alkenyl, alkynyl, hydroxy, alkoxy, alkylthio, sulfoxido,        sulfonyl, carboxy, ester, —CN, —NO₂, amino, and amido;    -   R⁶ is selected from H, halo, alkyl, hydroxy, alkoxy, alkylthio,        sulfoxido, sulfonyl, carboxy, ester, —CN, —NO₂, amino, amido,        sulfinamido, sulfonamido, heterocyclyl, heteroaryl,        poly(ethylene glycol), and methoxypoly(ethylene glycol), or    -   R⁶ and R⁷ together with atoms to which they are attached form a        cycloalkyl, heterocyclyl, aryl, or heteroaryl; and    -   each R⁹ is independently selected from halo, alkyl, —OH, alkoxy,        —CN, and amino.

In certain embodiments, when R² is C₁₋₆ alkyl, R⁶ is not C₁₋₆ alkyl orC₁₋₆ alkoxy. In other embodiments, when R² is C₁₋₃ alkyl, R⁶ is not C₁₋₃alkyl or C₁₋₃ alkoxy. In certain embodiments, when R² is ethyl, then R⁶is not methyl or methoxy.

In certain embodiments, provided is a compound of Formula (I′):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   n is 0, 1, 2, 3 or 4;    -   R¹ is selected from amino, aryl, cycloalkyl, heterocyclyl, and        heteroaryl;    -   R² is selected from halo, alkyl, alkenyl, alkynyl, alkoxy, —CN,        and —NO₂;    -   R⁵, R⁷ and R⁸ are each independently selected from H, halo,        alkyl, alkenyl, hydroxy, and alkoxy;    -   R⁶ is selected from halo, alkyl, alkenyl, alkynyl hydroxy,        alkoxy, alkylthio, sulfoxide, sulfonyl, carboxy, ester, —NO₂—CN,        amino, and amido; and    -   each R⁹ is independently selected from halo, hydroxy, and        alkoxy.

In certain embodiments, provided is a compound of Formula (I′):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   n is 0 or 1;    -   R¹ is selected from amino, heterocyclyl, and heteroaryl;    -   R² is selected from alkyl, alkoxy, —CN, and —NO₂;    -   R⁵, R⁷ and R⁸ are each independently selected from H and alkoxy;    -   R⁶ is selected from halo, alkyl, alkoxy, sulfoxido, sulfonyl,        carboxy, ester, —NO₂ and amido; and    -   each R⁹ is independently halo or alkoxy.

In certain embodiments, the compound of Formula (I′) described above hasat least one of the following:

1) R² is selected from C₂₋₃₀alkyl, —OH, C₁₋₃₀alkoxy, —NO₂, alkylthio,sulfoxido, sulfonyl, and amino, where

a) when R² is ethyl, then R⁶ is not methyl or methoxy, and/or

b) when R² is methoxy, then R⁶ is not halo, C₁₋₂ alkyl or C₁₋₂ alkoxy;

2) R¹ is heteroaryl, bridged heterocyclyl, fused heterocyclyl, orcycloheptyl;

3) R¹ is heterocyclyl substituted with one halo, amino, hydroxy, alkoxy,—CN, —NO₂, alkyl, carboxy, alkylthio, sulfoxido, sulfonyl, sulfinamido,sulfonamido, cycloalkyl, heterocyclyl, heteroaryl, poly(ethyleneglycol), and methoxypoly(ethylene glycol),

where if the substituent is alkyl, the alkyl is further substituted withone substituent selected from halo, amino, alkoxy, —CN, —NO₂, carboxy,ester, alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido,cycloalkyl, heterocyclyl, poly(ethylene glycol), methoxypoly(ethyleneglycol), pyrrolidinyl and piperidinyl; or the alkyl is substituted withat least one —OR³¹, wherein R³¹ is poly(ethylene glycol) ormethoxypoly(ethylene glycol);

4) R¹ is amino substituted with at least one substituent selected fromalkyl, cycloalkyl, heterocyclyl, heteroaryl, poly(ethylene glycol) ormethoxypoly(ethylene glycol) and amino,

where the alkyl is substituted with at least one substituent selectedfrom halo, amino, hydroxy, alkoxy, —CN, —NO₂, amido, carboxy, ester,alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido, cycloalkyl,heterocyclyl, and heteroaryl; or

5) R⁶ is alkyl substituted with at least one substituent selected fromhalo, amino, hydroxy, alkoxy, cycloalkoxy, heterocycloalkoxy, aryloxy,heteroaryloxy, poly(ethylene glycol)-oxy, methoxypoly(ethyleneglycol)-oxy, —CN, —NO₂, oxo, amido, carboxy, ester, alkylthio,sulfoxido, sulfonyl, sulfinamido, sulfonamido, heterocyclyl, cycloalkyl,aryl, heteroaryl, poly(ethylene glycol) and methoxypoly(ethyleneglycol).

In certain embodiments, R¹ is heterocyclyl substituted with at least onesubstituent selected from oxo, —OH, —OR²⁸, —N(R²⁸)₂, alkyl, aryl, andheterocyclyl, wherein the alkyl is substituted with at least onesubstituent selected from —N(R³¹)₂, —S(O)₀₋₂NR³¹R³¹, —C(O)N(R³¹)₂,heterocyclyl, cycloalkyl, pyrrolidinyl and piperidinyl; or the alkyl issubstituted with at least one —OR^(31a), wherein R^(31a) ispoly(ethylene glycol) or methoxypoly(ethylene glycol); and each R²⁸ andR³¹ are independently H or alkyl.

In certain embodiments, R¹ is heterocyclyl substituted with at least onesubstituent selected from oxo, —OH, —OR²⁸, —N(R²⁸)₂, —C(O)OR²⁸, alkyl,aryl, and heterocyclyl, wherein the alkyl is substituted with at leastone substituent selected from —OH, —N(R³¹)₂, —S(O)₀₋₂NR³¹R³¹,—C(O)N(R³¹)₂, heterocyclyl, cycloalkyl, pyrrolidinyl and piperidinyl; orthe alkyl is substituted with at least one —OR^(31a), wherein R^(31a) ispoly(ethylene glycol) or methoxypoly(ethylene glycol); and each R²⁸ andR³¹ are independently H or alkyl.

In certain embodiments, R¹ is —NR³R⁴, and R³ is H or alkyl unsubstitutedor substituted with at least one substituent selected from —OH,—N(R²⁸)₂, and heteroaryl, and R⁴ and R²⁸ are each independently H oralkyl.

In certain embodiments, R¹ is —NR³R⁴, and R³ is H or alkyl unsubstitutedor substituted with at least one substituent selected from —OH,—N(R²⁸)₂, aryl, and heteroaryl, and R⁴ and R²⁸ are each independently Hor alkyl.

In certain embodiments, a compound of Formula (I), or a compound ofFormula I and sub-formulae thereof, refers to a compound of Formula (I),and/or Formula (I′), and/or Formula (II) and/or (Formula III) and/orFormula (IV) and/or (Formula V) and/or Formula (VI) and/or Formula (VII)and/or Formula (VIII) and/or Formula (IX) and/or Formula (X) and/orFormula (XI) and/or Formula (XII), as described herein, or anycombination thereof.

In certain embodiments, provided is a compound of Formula (II):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of R¹, R², R⁵, R⁶, R⁷, and R⁸ is as defined herein.

In certain embodiments, provided is a compound of Formula (III):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of R¹, R², R⁵, R⁶, R⁷, R⁸ and R⁹ is as defined herein.

In certain embodiments, provided is a compound of Formula (IV):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of R¹, R², R⁵, R⁶, R⁷, R⁸ and R⁹ is as defined herein.

In certain embodiments, R¹ is heteroaryl or heterocyclyl, eachoptionally substituted with a second heterocyclyl, wherein the secondheterocyclyl is unsubstituted or substituted with one or moresubstituents, e.g., selected from —OH, —C(O)Oalkyl, —C(O)NHalkyl, alkyl,aryl, and heterocyclyl;

-   -   wherein the alkyl and heterocyclyl are each unsubstituted or        substituted with one or more substituents selected from —OH,        alkyl and aryl.

In certain embodiments, R¹ is heteroaryl, such as a 5- or 6-memberedheteroaryl. In certain embodiments, R¹ is heterocyclyl, such as a 5- to9-membered heterocyclyl, a 5- to 7-membered heterocyclyl, or a 5- to6-membered heterocyclyl.

In certain embodiments, R¹ is heterocyclyl, such as optionallysubstituted 5- to 7-membered heterocyclyl. In certain embodiments, oneof the heterocyclyl substituents is optionally further substituted witha second substituent selected from C₃₋₁₀ cycloalkyl and heterocyclyl. Insome embodiments, one heterocyclyl substituent is a sugar moiety, e.g.,a hexose. In certain embodiments, one of the second substituents isC₃₋₁₀ cycloalkyl or 5- to 7-membered heterocyclyl. In certainembodiments, one second substituent is 5- to 7-membered heterocyclyl. Insome embodiments, one second substituent is a sugar moiety, e.g., ahexose.

In certain embodiments, at least one heterocyclyl substituent is 5- to7-membered heterocyclyl. In certain embodiments, at least one secondsubstituent is selected from C₁₋₃₀ alkyl, 5- to 7-membered heterocyclyl,and phenyl.

In certain embodiments, R¹ is 5- to 7-membered heterocyclyl optionallysubstituted with one or two substituents, wherein at least onesubstituent is C₁₋₃₀alkyl. In certain embodiments, R¹ is 5- to7-membered heterocyclyl optionally substituted with one or twosubstituents, wherein at least one substituent is 5- to 7-memberedheterocyclyl. In some embodiments, the 5- to 7-membered heterocyclylsubstituent is further substituted with a sugar moiety, e.g., hexose.

In certain embodiments, R¹ is

wherein each s and t is independently 0, 1, 2 or 3, provided that thesum of s and t is 1, 2, 3, or 4; R²⁰ is selected from alkyl, cycloalkyl,heterocyclyl, aryl, and heteroaryl; and R^(20a) is H, NH₂, or OH.

In certain embodiments, R¹ is substituted by

In certain embodiments, R¹ is selected from:

In certain embodiments, R¹ is selected from

In certain embodiments, R¹ is selected from

In certain embodiments, R¹ is selected from

In certain embodiments, R¹ is selected from

In certain embodiments, R² is selected from C₁₋₆ alkyl, —NO₂, —OR¹⁸, andCN, wherein R¹⁸ is selected from C₁₋₁₆ alkyl, C₁₋₆haloalkyl, and C₁₋₆aminoalkyl. In certain embodiments, R² is selected from —CH₃, —CH₂CH₃,—CN, —NO₂, —OCF₃, and —OR¹⁸.

In certain embodiments, R² is —O(CH₂)_(m)CH₃, wherein m is an integerselected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 12, 13, 14, 15, and 16.

In certain embodiments, R² is amino. In some embodiments, the amino issubstituted with one or more substituents selected from alkyl,cycloalkyl, heterocyclyl, aryl, heteroaryl, and amino. In certainembodiments, the amino substituent is selected from cyclohexyl,piperazinyl, piperidinyl, and morpholinyl. In certain embodiments, theamino substituent is alkyl substituted with at least one substituentselected from —C(O)OH, —OH, phenyl and pyridyl, and the phenyl andpyridyl are each independently unsubstituted or substituted with halo,alkyl or OH.

In certain embodiments, R⁶ is selected from halo, alkyl, —OR¹⁷,—S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —NO₂, and —C(O)NR¹⁵R¹⁵;

R¹⁵ is selected from H, methyl, ethyl, iPr, —CH₂CH₂NEt₂, and —CH₂CH₂OH;R¹⁶ is methyl; andR¹⁷ is selected from methyl, trifluoromethyl and butyl.

In certain embodiments, R⁶ is halo, alkoxy or alkyl. In certainembodiments, R⁶ is F, alkyl or alkoxy. In certain embodiments, R⁶ is—OR¹⁷, and R¹⁷ is haloalkyl. In certain embodiments, R⁶ is selected from—CH₂CN, —OCF₃ and NO₂.

In certain embodiments, R⁶ is —SCH₃, —SOCH₃, or —SO₂CH₃. In certainembodiments, R⁶ is —S(O)₀₋₂R¹⁶. In certain embodiments, R⁶ is —S(O)R¹⁶.In certain embodiments, R⁶ is —S(O)₂R¹⁶. In certain embodiments, R⁶ is

In certain embodiments, R⁶ is

In certain embodiments, R⁶ is —C(O)OR¹⁵ where R¹⁵ is H or alkyl. Incertain embodiments, R⁶ is —C(O)OH, —C(O)OCH₃ or —C(O)OCH₂CH₃.

In certain embodiments, R⁶ is —C(O)NR¹⁵R¹⁵. In certain embodiments, eachR¹⁵ is independently selected from H, alkyl, and heterocyclyl. In otherembodiments, R⁶ is

In certain embodiments, one R¹⁵ is a sugar moiety. In certainembodiments, one R¹⁶ is a sugar moiety. In certain embodiments, R⁶ is asugar moiety. In certain embodiments, one or more of R⁶, R¹⁵, and R¹⁶ isa hexose.

In certain embodiments, R⁶ is selected from

In certain embodiments, provided is a compound of Formula (V):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof,

wherein

each of s, t, u, and v is independently 0, 1, 2, or 3, provided that thesum of s and t is 1, 2, 3 or 4, and the sum of u and v is 1, 2, 3 or 4;

w is 0, 1, 2, or 3;

Z¹ is C or N,

when Z¹ is C, R^(20a) is H, halo, oxo, —NH₂, —OH, —CN, —NO₂, —NHR²⁸,—N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH, —OC(O)R²⁸, —S(O)₀₋₂R²⁸,—NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂, —C(O)NHR²⁸,—C(O)N(R²⁸)₂, NHC(O)R²⁸, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,—NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, poly(ethylene glycol),methoxypoly(ethylene glycol), C₁₋₃₀ alkyl optionally substituted with OHor —C(O)OH, or C₁₋₃₀ heteroalkyl optionally substituted with OH or—C(O)OH, wherein R³² is H or C₁₋₄ alkyl, and R²⁸ is C₁₋₄ alkyl;

when Z¹ is N, R^(20a) is absent;

Z² is C or N;

Z³ is CH₂, CHR²⁵, CR²⁵R²⁵, or NR²⁵, O, or S(O)₀₋₂ and R²⁵ is selectedfrom H and alkyl; and

each of n, R², R⁵, R⁶, R⁷, R⁸, and R⁹ is as defined herein.

In certain embodiments, provided is a compound of Formula (V):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof,

wherein

each of s, t, u, and v is independently 0, 1, 2, or 3, provided that thesum of s and t is 1, 2, 3 or 4, and the sum of u and v is 1, 2, 3 or 4;

w is 0, 1, 2, or 3;

Z¹ is C or N,

when Z¹ is C, R^(20a) is H, halo, oxo, —NH₂, —OH, —CN, —NO₂, —OR²⁸,—NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH, —OC(O)R²⁸, —S(O)₀₋₂R²⁸,—NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂, —C(O)NHR²⁸,—C(O)N(R²⁸)₂, —NHC(O)R²⁸, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,—NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, poly(ethylene glycol),methoxypoly(ethylene glycol), C₁₋₃₀ alkyl optionally substituted with OHor —C(O)OH, or C₁₋₃₀ heteroalkyl optionally substituted with OH or—C(O)OH, wherein R³² is H or C₁₋₄ alkyl, and R²⁸ is C₁₋₄ alkyl;

when Z¹ is N, R^(20a) is absent;

Z² is C or N;

Z³ is CH₂, CHR²⁵, CR²⁵R²⁵, or NR²⁵, O, or S(O)₀₋₂ and R²⁵ is selectedfrom H and alkyl;

n is 0, 1, 2, 3 or 4;

R² is selected from H, halo, alkyl, alkenyl, alkynyl, —OH, alkoxy, —CN,—NO₂, alkylthio, sulfoxido, sulfonyl, and amino;

R⁵, R⁷ and R⁸ are each independently selected from H, halo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, alkylthio, sulfoxido, sulfonyl,carboxy, ester, —CN, —NO₂, amino, and amido;

R⁶ is selected from H, halo, alkyl, hydroxy, alkoxy, alkylthio,sulfoxido, sulfonyl, carboxy, ester, —CN, —NO₂, amino, amido,sulfinamido, sulfonamido, heterocyclyl, heteroaryl, poly(ethyleneglycol), and methoxypoly(ethylene glycol), or

R⁶ and R⁷ together with atoms to which they are attached form acycloalkyl, heterocyclyl, aryl, or heteroaryl; and

each R⁹ is independently selected from halo, alkyl, —OH, alkoxy, —CN,and amino.

In certain embodiments, s is 0 and t is 0. In certain embodiments, s is0 and t is 1. In certain embodiments, s is 1 and t is 1. In certainembodiments, s is 2 and t is 1. In certain embodiments, s is 3 and tis 1. In certain embodiments, s is 2 and t is 2.

In certain embodiments, w is 0. In certain embodiments, w is 1. Incertain embodiments, w is 2. In certain embodiments, w is 3.

In certain embodiments, u is 0 and v is 0. In certain embodiments, u is0 and v is 1. In certain embodiments, u is 1 and v is 1. In certainembodiments, u is 2 and v is 1. In certain embodiments, u is 3 and vis 1. In certain embodiments, s is 2 and u is 2.

In certain embodiments, provided is a compound of a formula (VI):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of n, s, u, v, R², R⁵, R⁶, R⁷, R⁸, R⁹, R^(20a), Z², and Z³ is asdefined herein.

In certain embodiments, provided is a compound of a formula (VII):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of n, s, u, v, R², R⁵, R⁶, R⁷, R⁸, R⁹, and Z³ is as defined herein.

In certain embodiments, provided is a compound of a formula (VIII):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of n, s, u, v, R², R⁵, R⁶, R⁷, R⁸, R⁹, R^(20a), Z², and Z³ is asdefined herein.

In certain embodiments, provided is a compound of a formula (IX):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of n, s, u, v, R², R⁵, R⁶, R⁷, R⁸, R⁹, Z², and Z³ is as definedherein.

In certain embodiments, provided is a compound of a formula (X):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of n, s, u, v, R², R⁵, R⁶, R⁷, R⁸, R⁹, R^(20a), Z², and Z³ is asdefined herein.

In certain embodiments, provided is a compound of a formula (XI):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of n, s, u, v, R², R⁵, R⁶, R⁷, R⁸, R⁹, Z², and Z³ is as definedherein.

In certain embodiments, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

R² is —OC₄₋₃₀ alkyl; and

each of n, R¹, R⁵, R⁶, R⁷, R⁸, and R⁹ is as defined herein.

In certain embodiments, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

R⁶ is —NO₂, ester, amido, alkylthio, sulfoxido, or sulfonyl; and

each of n, R¹, R⁵, R⁵, R⁷, R⁸, R⁹ is as defined herein.

In certain embodiments, R⁹ is —OH or —O—C₁₋₁₀ alkyl. In certainembodiments, each R⁹ is independently halo. In certain embodiments, n is1 or 2 and each R⁹ is independently halo. In certain embodiments, n is 1or 2 and each R⁹ is fluoro.

In certain embodiments, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;

wherein

R¹ is selected from —NR³R⁴, heterocyclyl optionally substituted with oneto five R²⁰, and heteroaryl optionally substituted with one to five R²¹;

R² is selected from H, halo, C₁₋₃₀ alkyl optionally substituted with oneto five R¹⁹, C₁₋₃₀ heteroalkyl optionally substituted with one to fiveR¹⁹, —OH, —OR¹⁸, —CN, —NO₂, —NH₂, —S(O)₀₋₂R¹⁸, and —NR¹¹R¹⁸;

R³ is selected from H, C₁₋₆ alkyl optionally substituted with one tofive R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁰,heterocyclyl optionally substituted with one to five R²⁰, aryloptionally substituted with one to five R²¹, and heteroaryl optionallysubstituted with one to five R²¹,

R⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with one tofive R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁰,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁰,heterocyclyl optionally substituted with one to five R²⁰, aryloptionally substituted with one to five R²¹, heteroaryl optionallysubstituted with one to five R²¹, poly(ethylene glycol),methoxypoly(ethylene glycol), and —NR¹³R¹⁴;

R⁵, R⁷ and R⁸ are each independently selected from H, halo, C₁₋₃₀ alkyloptionally substituted with one to five R²⁹, C₁₋₃₀ heteroalkyloptionally substituted with one to five R²⁹, —OR¹⁵, —S(O)₀₋₂R¹⁶,—C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂, —NR¹⁵R¹⁵, and —C(O)NR¹⁵R¹⁵;

R⁶ is selected from H, halo, C₁₋₃₀ alkyl optionally substituted with oneto five R²⁹, C₁₋₃₀ heteroalkyl optionally substituted with one to fiveR²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂, —NR¹⁵R¹⁵,—C(O)NR¹⁵R¹⁵, —NR¹⁵C(O)R¹⁶, S(O)₀₋₂NR¹⁵R¹⁵, —NR¹⁵S(O)₀₋₂R¹⁶,heterocyclyl optionally substituted with one to five R²⁹, heteroaryloptionally substituted with one to five R³⁰, poly(ethylene glycol), andmethoxypoly(ethylene glycol), or

R⁶ and R⁷ together with atoms to which they are attached form C₅₋₁₀cycloalkyl optionally substituted with one to five R²⁹, heterocyclyloptionally substituted with one to five R²⁹, aryl optionally substitutedwith one to five R³⁰, or heteroaryl optionally substituted with one tofive R³⁰;

R⁹ is independently selected from halo, C₁₋₈ alkyl optionallysubstituted with one to five R²², —OH, —OR¹⁰, —CN, and —NR¹¹R¹²;

n is 0, 1, 2, 3 or 4;

R¹⁰ is independently selected from C₁₋₁₀ alkyl optionally substitutedwith one to five R²², and C₃₋₁₀ cycloalkyl optionally substituted withone to five R²²;

R¹¹ and R¹² are each independently H or C₁₋₆ alkyl optionallysubstituted with one to five R²²;

R¹³ is selected from H, C₁₋₆ alkyl optionally substituted with one tofive R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁰,heterocyclyl optionally substituted with one to five R²⁰, aryloptionally substituted with one to five R²¹, and heteroaryl optionallysubstituted with one to five R²¹;

R¹⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with one tofive R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁰,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁰,heterocyclyl optionally substituted with one to five R²⁰, aryloptionally substituted with one to five R²¹, heteroaryl optionallysubstituted with one to five R²¹, poly(ethylene glycol), andmethoxypoly(ethylene glycol);

each R¹⁵ is independently selected from H, C₁₋₃₀ alkyl optionallysubstituted with one to five R²³, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²³, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²³, heterocyclyl optionally substitutedwith one to five R²³, aryl optionally substituted with one to five R²⁴,heteroaryl optionally substituted with one to five R²⁴, poly(ethyleneglycol), and methoxypoly(ethylene glycol);

R¹⁶ is selected from C₁₋₃₀ alkyl optionally substituted with one to fiveR²³, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²³,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²³,heterocyclyl optionally substituted with one to five R²³, aryloptionally substituted with one to five R²⁴, heteroaryl optionallysubstituted with one to five R²⁴, poly(ethylene glycol), andmethoxypoly(ethylene glycol);

R¹⁷ is selected from H, C₁₋₃₀ alkyl optionally substituted with one tofive R²⁷, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁷,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁷,heterocyclyl optionally substituted with one to five R²⁷, aryloptionally substituted with one to five R²⁴, heteroaryl optionallysubstituted with one to five R²⁴, poly(ethylene glycol), andmethoxypoly(ethylene glycol);

R¹⁸ is selected from C₁₋₃₀ alkyl optionally substituted with one to fiveR¹⁹ and C₁₋₃₀ heteroalkyl optionally substituted with one to five R¹⁹;

each R²⁰ is independently selected from halo, oxo, —NH₂, —OH, —CN, —NO₂,—OR²⁸, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH, —OC(O)R²⁸,—S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂,—C(O)NHR²⁸, —C(O)N(R²⁸)₂, —NHC(O)R²⁸, —OC(O)NHR²⁸, —NHC(O)OR²⁸,—OC(O)N(R²⁸)₂, —NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀alkyl optionally substituted with one to five R²⁵, C₁₋₃₀ heteroalkyloptionally substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²⁵, heterocyclyl optionally substitutedwith one to five R²⁵, aryl optionally substituted with one to five R²⁶,heteroaryl optionally substituted with one to five R²⁶, poly(ethyleneglycol), and methoxypoly(ethylene glycol);

each R²¹ is independently selected from halo, —NH₂, —OH, —CN, —NO₂,—OR²⁸, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH, —OC(O)R²⁸,—S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸,—NHC(O)R²⁸, —C(O)N(R²⁸)₂, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,—NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₆ alkyl optionallysubstituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²⁵, heterocyclyl optionally substitutedwith one to five R²⁵, aryl optionally substituted with one to five R²⁶,and heteroaryl optionally substituted with one to five R²⁶,poly(ethylene glycol), and methoxypoly(ethylene glycol);

each R¹⁹ or R²² is independently selected from halo, —NH₂, —OH, —CN,—NO₂, oxo, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy,—NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)O—C₁₋₄ alkyl,—C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl, —S(O)₀₋₂NH—C₁₋₄alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl, —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl,—C(O)N(C₁₋₄ alkyl)₂, —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl,—OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂,—C(O)—C₁₋₄ haloalkyl, —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄haloalkyl, —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,—C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄ haloalkyl)₂,—OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl, —OC(O)N(C₁₋₄haloalkyl)₂, and C₃₋₁₀ cycloalkyl;

each R²⁵ is independently selected from halo, —NH₂, —OH, —CN, —NO₂, oxo,—NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH, —S(O)₀₋₂R³¹,—NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹, —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂,—C(O)NHR³¹, —NR³²C(O)R³¹, —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹,—OC(O)N(R³¹)₂, —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀alkyl optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyloptionally substituted with one to five R³³, C₃ to cycloalkyl optionallysubstituted with one to five R³³, heterocyclyl optionally substitutedwith one to five R³³, aryl optionally substituted with one to five R³⁴,heteroaryl optionally substituted with one to five R³⁴, poly(ethyleneglycol), and methoxypoly(ethylene glycol);

each R²⁶ is independently selected from halo, —NH₂, —OH, —CN, —NO₂,—NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH, —S(O)₀₋₂R³¹,—NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹, —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂,—C(O)NHR³¹, —NR³²C(O)R³¹, —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹,—OC(O)N(R³¹)₂, —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀alkyl optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyloptionally substituted with one to five R³³, C₃ to cycloalkyl optionallysubstituted with one to five R³³, heterocyclyl optionally substitutedwith one to five R³³, aryl optionally substituted with one to five R³⁴,and heteroaryl optionally substituted with one to five R³⁴,poly(ethylene glycol), and methoxypoly(ethylene glycol);

each R³¹ is independently selected C₁₋₃₀ alkyl optionally substitutedwith one to five R³³, C₁₋₃₀ heteroalkyl optionally substituted with oneto five R³³, C₃₋₁₀ cycloalkyl optionally substituted with one to fiveR³³, heterocyclyl optionally substituted with one to five R³³, aryloptionally substituted with one to five R³⁴, heteroaryl optionallysubstituted with one to five R³⁴, poly(ethylene glycol) andmethoxypoly(ethylene glycol);

each R³² is independently selected H and C₁₋₄ alkyl;

each R²³, R²⁷, R²⁹ or R³³ is independently selected from halo, —NH₂,—OH, —CN, —NO₂, oxo, C₁₋₄ alkyl optionally substituted with phenyl, C₁₋₄haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)O—C₁₋₄ alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂ NH—C₁₋₄alkyl, —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,—OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl, —S(O)₀₋₂—C₁₋₄haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl, —S(O)₀₋₂NH—C₁₋₄ haloalkyl,—NHS(O)₀₋₂NH—C₁₋₄ haloalkyl, —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄haloalkyl, —C(O)N(C₁₋₄ haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl,—NHC(O)O—C₁₋₄ haloalkyl, —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl,heterocyclyl, aryl heteroaryl, —(CH₂)₁₋₃₀—C(O)OH,—(CH₂)₀₋₄—O-poly(ethylene glycol), methoxypoly(ethyleneglycol)-O—(CH₂)₀₋₄—, and sugar moiety;

each R²⁴, R³⁰ or R³⁴ is independently selected from halo, —NH₂, —OH,—CN, —NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy,—NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)OH, —C(O)O—C₁₋₄alkyl, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄₀ alkyl, —S(O)₀₋₂NH—C₁₋₄alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl, —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl,—C(O)N(C₁₋₄ alkyl)₂, —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl,—OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂,—C(O)—C₁₋₄ haloalkyl, —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄₀haloalkyl, —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,—C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄ haloalkyl)₂,—OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl, —OC(O)N(C₁₋₄haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl, heteroaryl,—(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene glycol),—(CH₂)₀₋₄—O-methoxypoly(ethylene glycol) and sugar moiety; and

each R²⁸ is independently selected from C₁₋₃₀ alkyl optionallysubstituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²⁵, heterocyclyl optionally substitutedwith one to five R²⁵, aryl optionally substituted with one to five R²⁶,heteroaryl optionally substituted with one to five R²⁶, poly(ethyleneglycol), and methoxypoly(ethylene glycol).

In certain embodiments, provided is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;

wherein

n is 0, 1, 2, 3 or 4;

R¹ is selected from —NR³R⁴, heterocyclyl optionally substituted with oneto five R²⁰, and heteroaryl optionally substituted with one to five R²¹;

R² is selected from H, halo, C₁₋₃₀ alkyl optionally substituted with oneto five R¹⁹, C₁₋₃₀ heteroalkyl optionally substituted with one to fiveR¹⁹, —OH, —OR¹⁸, —CN, —NO₂, —S(O)₀₋₂R¹⁸, and —NR¹¹R¹⁸;

R³ is selected from H, C₁₋₆ alkyl optionally substituted with one tofive R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁰,heterocyclyl optionally substituted with one to five R²⁰, aryloptionally substituted with one to five R²¹, and heteroaryl optionallysubstituted with one to five R²¹;

R⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with one tofive R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁰,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁰,heterocyclyl optionally substituted with one to five R²⁰, aryloptionally substituted with one to five R²¹, heteroaryl optionallysubstituted with one to five R²¹, poly(ethylene glycol),methoxypoly(ethylene glycol), and —NR¹³R¹⁴;

R⁵, R⁷ and R⁸ are each independently selected from H, halo, C₁₋₃₀ alkyloptionally substituted with one to five R²⁹, C₁₋₃₀ heteroalkyloptionally substituted with one to five R²⁹, —OR¹⁵, —S(O)₀₋₂R¹⁶,—C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂, —NR¹⁵R¹⁵, and —C(O)NR¹⁵R¹⁵;

R⁶ is selected from H, halo, C₁₋₃₀ alkyl optionally substituted with oneto five R²⁹, C₁₋₃₀ heteroalkyl optionally substituted with one to fiveR²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂, —NR¹⁵R¹⁵,—C(O)NR¹⁵R¹⁵, —NR¹⁵C(O)R¹⁶, —S(O)₀₋₂NR¹⁵R¹⁵, —NR¹⁵S(O)₀₋₂R¹⁶,heterocyclyl optionally substituted with one to five R²⁹, heteroaryloptionally substituted with one to five R³⁰, poly(ethylene glycol), andmethoxypoly(ethylene glycol), or

R⁶ and R⁷ together with atoms to which they are attached form C₅₋₁₀cycloalkyl optionally substituted with one to five R²⁹, heterocyclyloptionally substituted with one to five R²⁹, aryl optionally substitutedwith one to five R³⁰, or heteroaryl optionally substituted with one tofive R³⁰;

R⁹ is independently selected from halo, C₁₋₈ alkyl optionallysubstituted with one to five R²², —OH, —OR¹⁰, —CN, and —NR¹¹R¹²;

R¹⁰ is independently selected from C₁₋₁₀ alkyl optionally substitutedwith one to five R²², and C₃₋₁₀ cycloalkyl optionally substituted withone to five R²²;

R¹¹ and R¹² are each independently H or C₁₋₆ alkyl optionallysubstituted with one to five R²²;

R¹³ is selected from H, C₁₋₆ alkyl optionally substituted with one tofive R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁰,heterocyclyl optionally substituted with one to five R²⁰, aryloptionally substituted with one to five R²¹, and heteroaryl optionallysubstituted with one to five R²¹;

R¹⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with one tofive R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁰,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁰,heterocyclyl optionally substituted with one to five R²⁰, aryloptionally substituted with one to five R²¹, heteroaryl optionallysubstituted with one to five R²¹, poly(ethylene glycol), andmethoxypoly(ethylene glycol);

each R¹⁵ is independently selected from H, C₁₋₃₀ alkyl optionallysubstituted with one to five R²³, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²³, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²³, heterocyclyl optionally substitutedwith one to five R²³, aryl optionally substituted with one to five R²⁴,heteroaryl optionally substituted with one to five R²⁴, poly(ethyleneglycol), and methoxypoly(ethylene glycol);

R¹⁶ is selected from C₁₋₃₀ alkyl optionally substituted with one to fiveR²³, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²³,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²³,heterocyclyl optionally substituted with one to five R²³, aryloptionally substituted with one to five R²⁴, heteroaryl optionallysubstituted with one to five R²⁴, poly(ethylene glycol), andmethoxypoly(ethylene glycol);

R¹⁷ is selected from H, C₁₋₃₀ alkyl optionally substituted with one tofive R²⁷, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁷,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁷,heterocyclyl optionally substituted with one to five R²⁷, aryloptionally substituted with one to five R²⁴, heteroaryl optionallysubstituted with one to five R²⁴, poly(ethylene glycol), andmethoxypoly(ethylene glycol);

R¹⁸ is selected from C₁₋₃₀ alkyl optionally substituted with one to fiveR¹⁹ and C₁₋₃₀ heteroalkyl optionally substituted with one to five R¹⁹;

each R²⁰ is independently selected from halo, oxo, —NH₂, —OH, —CN, —NO₂,—NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH, —OC(O)R²⁸, —S(O)₀₋₂R²⁸,—NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂, —C(O)NHR²⁸,—C(O)N(R²⁸)₂, —NHC(O)R²⁸, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,—NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl optionallysubstituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²⁵, heterocyclyl optionally substitutedwith one to five R²⁵, aryl optionally substituted with one to five R²⁶,heteroaryl optionally substituted with one to five R²⁶, poly(ethyleneglycol), and methoxypoly(ethylene glycol);

each R²¹ is independently selected from halo, —NH₂, —OH, —CN, —NO₂,—OR²⁸, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH, —OC(O)R²⁸,—S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸,—NHC(O)R²⁸, —C(O)N(R²⁸)₂, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,—NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₆ alkyl optionallysubstituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²⁵, heterocyclyl optionally substitutedwith one to five R²⁵, aryl optionally substituted with one to five R²⁶,and heteroaryl optionally substituted with one to five R²⁶,poly(ethylene glycol), and methoxypoly(ethylene glycol);

each R¹⁹ or R²² is independently selected from halo, —NH₂, —OH, —CN,—NO₂, oxo, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy,—NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)O—C₁₋₄ alkyl,—C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl, —S(O)₀₋₂NH—C₁₋₄alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl, —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl,—C(O)N(C₁₋₄ alkyl)₂, —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl,—OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂,—C(O)—C₁₋₄ haloalkyl, —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄haloalkyl, —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,—C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄ haloalkyl)₂,—OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl, —OC(O)N(C₁₋₄haloalkyl)₂, and C₃₋₁₀ cycloalkyl;

each R²⁵ is independently selected from halo, —NH₂, —OH, —CN, —NO₂, oxo,—OR³¹, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH, —S(O)₀₋₂R³¹,—NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹, —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂,—C(O)NHR³¹, —NR³²C(O)R³¹, —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹,—OC(O)N(R³¹)₂, —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀alkyl optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyloptionally substituted with one to five R³³, C₃ to cycloalkyl optionallysubstituted with one to five R³³, heterocyclyl optionally substitutedwith one to five R³³, aryl optionally substituted with one to five R³⁴,and heteroaryl optionally substituted with one to five R³⁴,poly(ethylene glycol), and methoxypoly(ethylene glycol);

each R²⁶ is independently selected from halo, —NH₂, —OH, —CN, —NO₂,—OR³¹, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH, —S(O)₀₋₂R³¹,—NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹, —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂,—C(O)NHR³¹, —NR³²C(O)R³¹, —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹,—OC(O)N(R³¹)₂, —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀alkyl optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyloptionally substituted with one to five R³³, C₃ to cycloalkyl optionallysubstituted with one to five R³³, heterocyclyl optionally substitutedwith one to five R³³, aryl optionally substituted with one to five R³⁴,heteroaryl optionally substituted with one to five R³⁴, poly(ethyleneglycol), and methoxypoly(ethylene glycol);

each R³¹ is independently selected C₁₋₃₀ alkyl optionally substitutedwith one to five R³³, C₁₋₃₀ heteroalkyl optionally substituted with oneto five R³³, C₃₋₁₀ cycloalkyl optionally substituted with one to fiveR³³, heterocyclyl optionally substituted with one to five R³³, aryloptionally substituted with one to five R³⁴, heteroaryl optionallysubstituted with one to five R³⁴, poly(ethylene glycol) andmethoxypoly(ethylene glycol);

each R³² is independently selected H and C₁₋₄ alkyl;

each R²³, R²⁷, R²⁹ or R³³ is independently selected from halo, —NH₂,—OH, —CN, —NO₂, oxo, C₁₋₄ alkyl optionally substituted with phenyl, C₁₋₄haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)O—C₁₋₄ alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄alkyl, —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,—OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄haloalkyl, —N(C₁₋₄haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,—S(O)₀₋₂—C₁₋₄haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,—S(O)₀₋₂NH—C₁₋₄haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl, —C(O)NH—C₁₋₄haloalkyl, —NHC(O)—C₁₋₄haloalkyl, —C(O)N(C₁₋₄haloalkyl)₂, —OC(O)NH—C₁₋₄haloalkyl, —NHC(O)O—C₁₋₄haloalkyl, —OC(O)N(C₁₋₄haloalkyl)₂, C₃₋₁₀cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH₂)₁₋₃₀—C(O)OH,—(CH₂)₀₋₄—O-poly(ethylene glycol), methoxypoly(ethyleneglycol)-O—(CH₂)₀₋₄—, and sugar moiety;

each R²⁴, R³⁰ or R³⁴ is independently selected from halo, —NH₂, —OH,—CN, —NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy,—NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)OH, —C(O)O—C₁₋₄alkyl, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl, —S(O)₀₋₂NH—C₁₋₄alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl, —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl,—C(O)N(C₁₋₄ alkyl)₂, —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl,—OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄haloalkyl, —N(C₁₋₄haloalkyl)₂,—C(O)—C₁₋₄haloalkyl, —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,—S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄haloalkyl, —C(O)NH—C₁₋₄haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄haloalkyl)₂,—OC(O)NH—C₁₋₄haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,—OC(O)N(C₁₋₄haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl,heteroaryl, —(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene glycol),—(CH₂)₀₋₄—O-methoxypoly(ethylene glycol) and sugar moiety; and

each R²⁸ is independently selected from C₁₋₃₀ alkyl optionallysubstituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²⁵, heterocyclyl optionally substitutedwith one to five R²⁵, aryl optionally substituted with one to five R²⁶,heteroaryl optionally substituted with one to five R²⁶, poly(ethyleneglycol), and methoxypoly(ethylene glycol).

In certain embodiments, the compound of Formula (I) described above hasat least one of the following:

-   -   (1) R² is selected from C₂₋₃₀ alkyl optionally substituted with        one to five R¹⁹, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R¹⁹, —NO₂, —OR¹⁸, —S(O)₀₋₂CH₃, —S(O)₀₋₂R¹⁸, —NH₂,        —NHCH₃, and —NR¹¹R¹⁸, wherein R¹⁸ is selected from C₁₋₃₀        haloalkyl, C₂₋₃₀ alkyl optionally substituted with one to five        R¹⁹ and C₂₋₃₀ heteroalkyl optionally substituted with one to        five R¹⁹; wherein when R² is ethyl, then R⁶ is not methyl or        methoxy;    -   (2) R¹ is heteroaryl optionally substituted with one to five        R²¹, or fused heterocyclyl optionally substituted with one to        five R²⁰;    -   (3) R¹ is heterocyclyl substituted with at least one R²⁰        selected from halo, oxo, —NH₂, —OH, —CN, —NO₂, —NHR²⁸, —N(R²⁸)₂,        —C(O)R²⁸, —C(O)OR^(28a), —NHS(O)₀₋₂R²⁸, —OC(O)R²⁸, —S(O)₀₋₂R²⁸,        —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸,        —C(O)N(R²⁸)₂, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl substituted with        one to five R²⁵, heteroaryl optionally substituted with one to        five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);        -   wherein            -   the C₁₋₃₀ alkyl is substituted with at least one R²⁵                selected from halo, —NH₂, —OH, —CN, —NO₂, oxo, —NHR³¹,                —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH, —S(O)₀₋₂R³¹,                —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹, —NR³²S(O)₀₋₂NR³²R³¹,                —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹, —C(O)N(R³¹)₂,                —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂, —NR³²C(O)NH₂,                —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl optionally                substituted with one to five R³³, C₁₋₃₀ heteroalkyl                optionally substituted with one to five R³³,                heterocyclyl substituted with one to five R³³,                poly(ethylene glycol), methoxypoly(ethylene glycol),                pyrrolidinyl and piperidinyl; or the C₁₋₃₀ alkyl is                substituted with at least one —OR^(31a), wherein R^(31a)                is poly(ethylene glycol) or methoxypoly(ethylene                glycol);            -   R^(28a) is selected from C₁₋₃₀ alkyl substituted with                one to five R²⁵, C₁₋₃₀ heteroalkyl optionally                substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl                optionally substituted with one to five R²⁵,                heterocyclyl optionally substituted with one to five                R²⁵, aryl optionally substituted with one to five R²⁶,                heteroaryl optionally substituted with one to five R²⁶,                poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   (4) R¹ is —NR³R⁴, and R⁴ is selected from C₁₋₃₀ alkyl        substituted with one to five R²⁰, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁰, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁰, heterocyclyl optionally        substituted with one to five R²⁰, heteroaryl optionally        substituted with one to five R²¹, poly(ethylene glycol),        methoxypoly(ethylene glycol), and —NR¹³R¹⁴,        -   wherein            -   the C₁₋₃₀ alkyl is substituted with at least one R²⁰                selected from halo, —NH₂, —OH, —CN, —NO₂, —NHR²⁸,                —N(R²⁸)₂, —C(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸,                —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸,                —C(O)N(R²⁸)₂, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,                C₃₋₁₀ cycloalkyl optionally substituted with one to five                R²⁵, heterocyclyl optionally substituted with one to                five R²⁵, and heteroaryl optionally substituted with one                to five R²⁶; or    -   (5) R⁶ is selected from C₁₋₆ alkyl substituted with one to five        R²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, C(O)OR¹⁵, —OC(O)R¹⁶, —NO₂, —NR¹⁵R¹⁵,        —C(O)NR¹⁵R¹⁵, —S(O)₀₋₂NHR¹⁶, —NHS(O)₀₋₂R¹⁶, heterocyclyl        optionally substituted with one to five R²⁹, heteroaryl        optionally substituted with one to five R³⁰, poly(ethylene        glycol), and methoxypoly(ethylene glycol), wherein R¹⁷ is        selected from C₁₋₃₀ alkyl substituted with one to five R²⁷,        C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁷,        C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁷,        heterocyclyl optionally substituted with one to five R²⁷, aryl        optionally substituted with one to five R²⁴, heteroaryl        optionally substituted with one to five R²⁴, poly(ethylene        glycol), and methoxypoly(ethylene glycol).

In certain embodiments, R¹ is heteroaryl optionally substituted with oneto five R²¹; or

-   -   R¹ is heterocyclyl substituted with at least one R²⁰ selected        from halo, oxo, —NH₂, —OH, —CN, —NO₂, —OR²⁸, —NHR²⁸, —N(R²⁸)₂,        —C(O)R²⁸, —C(O)OR^(28a), —NHS(O)₀₋₂R²⁸, —OC(O)R²⁸, —S(O)₀₋₂R²⁸,        —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸,        —C(O)N(R²⁸)₂, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, heterocyclyl substituted with        one to five R²⁵, poly(ethylene glycol), and methoxypoly(ethylene        glycol);        -   wherein            -   the C₁₋₃₀ alkyl is substituted with at least one R²⁵                selected from halo, —NH₂, —OH, —CN, —NO₂, oxo, —NHR³¹,                —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH, —S(O)₀₋₂R³¹,                —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹, —NR³²S(O)₀₋₂NR³²R³¹,                —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹, —C(O)N(R³¹)₂,                —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂, —NR³²C(O)NH₂,                —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl optionally                substituted with one to five R³³, C₁₋₃₀ heteroalkyl                optionally substituted with one to five R³³,                heterocyclyl substituted with one to five R³³,                poly(ethylene glycol), methoxypoly(ethylene glycol),                pyrrolidinyl and piperidinyl; or the C₁₋₃₀ alkyl is                substituted with at least one —OR³¹, wherein R³¹ is                poly(ethylene glycol) or methoxypoly(ethylene glycol);                and            -   R^(28a) is selected from C₁₋₃₀ alkyl substituted with                one to five R²⁵, C₁₋₃₀ heteroalkyl optionally                substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl                optionally substituted with one to five R²⁵,                heterocyclyl optionally substituted with one to five                R²⁵, aryl optionally substituted with one to five R²⁶,                heteroaryl optionally substituted with one to five R²⁶,                poly(ethylene glycol), and methoxypoly(ethylene glycol).

In certain embodiments, R¹ is heteroaryl optionally substituted with oneto five R²¹. In certain embodiments, R¹ is 5- or 6-membered heteroaryloptionally substituted with one to five R²¹.

In certain embodiments, R¹ is heterocyclyl optionally substituted withone to two R²⁰. In certain embodiments, R¹ is 5- to 7-memberedheterocyclyl optionally substituted with one to two R²⁰. In certainembodiments, one of the R²⁰ is optionally substituted with one to fiveR²⁵, C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁵,C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁵, orheterocyclyl optionally substituted with one to five R²⁵. In someembodiments, one R²⁰ is a sugar moiety. In certain embodiments, one ofthe R²⁵ is C₃₋₁₀ cycloalkyl optionally substituted with one to five R³³,or 5- to 7-membered heterocyclyl optionally substituted with one to fiveR³³. In some embodiments, one R²⁵ is a sugar moiety. In certainembodiments, one of the R³³ is 5- to 7-membered heterocyclyl. In someembodiments, one R³³ is a sugar moiety.

In certain embodiments, at least one R²⁰ is 5- to 7-memberedheterocyclyl optionally substituted with one to five R²⁵. In certainembodiments, at least one R²⁵ is selected from C₁₋₃₀ alkyl optionallysubstituted with one to five R³³, 5- to 7-membered heterocyclyloptionally substituted with one to five R³³, and phenyl optionallysubstituted with one to five R³⁴. In some embodiments, one R²⁰ is asugar moiety.

In certain embodiments, R¹ is 5- to 7-membered heterocyclyl optionallysubstituted with one to two R²⁰, wherein at least one R²⁰ is C₁₋₃₀ alkyloptionally substituted with one to five R²⁵. In certain embodiments, R¹is 5- to 7-membered heterocyclyl optionally substituted with one to twoR²⁰, wherein at least one R²⁰ is 5- to 7-membered heterocyclyloptionally substituted with one to five R²⁵. In some embodiments, atleast one R²⁵ is 5- to 7-membered heterocyclyl optionally substitutedwith one to five R³³. In some embodiments, one R²⁵ is a sugar moiety.

In certain embodiments, R¹ is

wherein each s and t is independently 0, 1, 2 or 3, provided that thesum of s and t is 1, 2, 3, or 4, R²⁰ is C₁₋₃₀ alkyl substituted with oneto five R²⁵, C₁₋₃₀ heteroalkyl optionally substituted with one to fiveR²⁵, C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁵,heterocyclyl optionally substituted with one to five R²⁵, aryloptionally substituted with one to five R²⁶, heteroaryl optionallysubstituted with one to five R²⁶, and R^(20a) is H, NH₂, or OH.

In certain embodiments, R²⁰ is selected from —S(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,—NHS(O)₀₋₂NHR²⁸, C₁₋₃₀ alkyl substituted with one to five R²⁵,heterocyclyl optionally substituted with one to five R²⁵, and heteroaryloptionally substituted with one to five R²⁶. In some embodiments, oneR²⁰ is a sugar moiety.

In certain embodiments, one of R²⁵ is selected from C₁₋₃₀ alkylsubstituted with one to five R³³, heterocyclyl optionally substitutedwith one to five R³³, and heteroaryl optionally substituted with one tofive R³³. In some embodiments, one R²⁵ is a sugar moiety. In certainembodiments, one of R²⁶ is selected from C₁₋₃₀ alkyl substituted withone to five R³³, heterocyclyl optionally substituted with one to fiveR³³, and heteroaryl optionally substituted with one to five R³³. In someembodiments, one R²⁶ is a sugar moiety.

In certain embodiments, one R²¹ is a sugar moiety. In certainembodiments, one R²⁸ is a sugar moiety. In certain embodiments, one R³¹is a sugar moiety.

In certain embodiments, one R²³, R²⁴, R²⁷, R²⁹, R³⁰, R³³ or R³⁴ is asugar moiety.

In certain embodiments, both R² and R⁶ are other than H. In certainembodiments, when R² is methyl or ethyl, then R⁶ is not selected frommethyl, ethyl, methoxy or ethoxy.

In certain embodiments, R² is selected from C₂₋₃₀ alkyl optionallysubstituted with one to five R¹⁹, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R¹⁹, —NO₂, —S(O)₀₋₂R¹⁸, and —NR¹¹R¹⁸,wherein R¹⁸ is selected from C₁₋₃₀haloalkyl, C₂₋₃₀ alkyl optionallysubstituted with one to five R¹⁹ and C₂₋₃₀ heteroalkyl optionallysubstituted with one to five R¹⁹; wherein when R² is ethyl, then R⁶ isnot methyl or methoxy.

In certain embodiments, R² is C₂₋₃₀ alkyl substituted with one to fiveR¹⁹. In certain embodiments, R² is C₂₋₃₀ heteroalkyl substituted withone to five R¹⁹. In certain embodiments, R² is —O(CH₂)_(m)CH₃ or—O(CH₂)_(m)CH₂C(O)OH, wherein m is an integer selected from 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, and 29.

In certain embodiments, R² is —NO₂. In certain embodiments, R² is —CN.

In certain embodiments, R² is —OR¹⁸ or —S(O)₀₋₂R¹⁸. In certainembodiments, R¹⁸ is C₁₋₃₀haloalkyl. In certain embodiments, R¹⁸ is C₂₋₃₀alkyl optionally substituted with one to five R¹⁹. In certainembodiments, R¹⁸ is C₁₋₃₀ heteroalkyl optionally substituted with one tofive R¹⁹.

In certain embodiments, each R¹⁹ is independently selected from halo,—NH₂, —OH, —CN, —NO₂, oxo, C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂,—C(O)—C₁₋₄ alkyl, and —C(O)OH. In certain embodiments, R¹⁹ is —C(O)OH.

In certain embodiments, R² is C₁₋₃₀ alkyl, —CN, —NO₂ and —OR¹⁸. Incertain embodiments, R² is —CH₃, —CH₂CH₃, —NO₂, —OCF₃, and —OR¹⁸. Incertain embodiments, R² is —OR¹⁸, wherein R¹⁸ is C₄₋₃₀ alkyl optionallysubstituted with one to five R¹⁹.

In certain embodiments, R⁶ is selected from C₁₋₆ alkyl substituted withone to five R²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —NO₂,—NR¹⁵R¹⁵, —C(O)NR¹⁵R¹⁵, —S(O)₀₋₂NHR¹⁶, —NHS(O)₀₋₂R¹⁶, heterocyclyloptionally substituted with one to five R²⁹, heteroaryl optionallysubstituted with one to five R³⁰, poly(ethylene glycol), andmethoxypoly(ethylene glycol), wherein R¹⁷ is selected from C₁₋₃₀ alkylsubstituted with one to five R²⁷, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²⁷, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²⁷, heterocyclyl optionally substitutedwith one to five R²⁷, aryl optionally substituted with one to five R²⁴,heteroaryl optionally substituted with one to five R²⁴, poly(ethyleneglycol), and methoxypoly(ethylene glycol).

In certain embodiments, R⁶ is a sugar moiety.

In certain embodiments, R⁶ is halo, C₁₋₃₀ alkyl optionally substitutedwith one to five R²⁹, C₁₋₃₀ heteroalkyl optionally substituted with oneto five R²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —NO₂, —NR¹⁵R¹⁵,—C(O)NR¹⁵R¹⁵, —NR¹⁵C(O)R¹⁶, —S(O)₀₋₂NR¹⁵R¹⁵, —NR¹⁵S(O)₀₋₂R¹⁶,heterocyclyl optionally substituted with one to five R²⁹, heteroaryloptionally substituted with one to five R³⁰, poly(ethylene glycol), andmethoxypoly(ethylene glycol).

In certain embodiments, R⁶ is halo, OR¹⁷, or C₁₋₃₀ alkyl optionallysubstituted with halo or C(O)OH, wherein R¹⁷ is C₁₋₃₀ alkyl optionallysubstituted with halo or C(O)OH. In certain embodiments, R⁶ is F, C₁-C₄alkyl or C₁-C₄ alkoxy. In certain embodiments, R⁶ is OR¹⁷, and R¹⁷ isC₁-C₄ haloalkyl. In certain embodiments, R⁶ is selected from CH₂CN, OCF₃and NO₂.

In certain embodiments, R⁶ is S(O)₀₋₂R¹⁶. In certain embodiments, R¹⁶ isC₁-C₃₀ alkyl optionally substituted with halo or C(O)OH. In certainembodiments, R⁶ is SCH₃, SOCH₃, and SO₂CH₃. In certain embodiments, R⁶is —SCH₃, —SOCH₃, or —SO₂CH₃. In certain embodiments, R⁶ is —S(O)₀₋₂R¹⁶.In certain embodiments, R⁶ is —S(O)R¹⁶. In certain embodiments, R⁶ is—S(O)₂R¹⁶. In certain embodiments, R⁶ is

In certain embodiments, R⁶ is

In certain embodiments, R⁶ is C(O)OR¹⁵. In certain embodiments, R¹⁵ is Hor C₁₋₃₀ alkyl optionally substituted with halo or C(O)OH. In certainembodiments, R⁶ is —C(O)OH, —C(O)OCH₃ or —C(O)OCH₂CH₃.

In certain embodiments, R⁶ is —C(O)NR¹⁵R¹⁵. In certain embodiments, oneR¹⁵ is H or alkyl. In certain embodiments, one R¹⁵ is H, C₁₋₃₀ alkyloptionally substituted with one to five R²³, C₁₋₃₀ heteroalkyloptionally substituted with one to five R²⁰, and heterocyclyl optionallysubstituted with one to five R²³.

In certain embodiments, one R¹⁵ is a sugar moiety. In certainembodiments, one R¹⁶ is a sugar moiety.

In certain embodiments, R⁶ is a sugar moiety.

In certain embodiments, R⁶ and R⁷ together with atoms to which they areattached form C₅₋₁₀ cycloalkyl optionally substituted with one to fiveR²⁹. In certain embodiments, R⁶ and R⁷ together with atoms to which theyare attached form heterocyclyl optionally substituted with one to fiveR²⁹. In certain embodiments, R⁶ and R⁷ together with atoms to which theyare attached form aryl optionally substituted with one to five R³⁰. Incertain embodiments, R⁶ and R⁷ together with atoms to which they areattached form heteroaryl optionally substituted with one to five R³⁰. Incertain embodiments, one R²⁹ is a sugar moiety. In certain embodiments,one R³⁰ is a sugar moiety.

In certain embodiments, R⁵, R⁷ and R⁸ are each H. In certainembodiments, R⁵ and R⁸ are each H, and R⁷ is OCH₃.

In certain embodiments, the compound has no more than one group selectedfrom poly(ethylene glycol), methoxypoly(ethylene glycol) and sugarmoiety.

In certain embodiments, both R² and R⁶ are other than H. In certainembodiments, when R² is methyl or ethyl, then R⁶ is not selected frommethyl, ethyl, methoxy or ethoxy.

In certain embodiments, R² is selected from C₂₋₃₀ alkyl optionallysubstituted with one to five R¹⁹, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R¹⁹, —NO₂, —S(O)₀₋₂R¹⁸, and —NR¹¹R¹⁸,wherein R¹⁸ is selected from C₁₋₃₀haloalkyl, C₂₋₃₀ alkyl optionallysubstituted with one to five R¹⁹ and C₂₋₃₀ heteroalkyl optionallysubstituted with one to five R¹⁹; wherein when R² is ethyl, then R⁶ isnot methyl or methoxy.

In certain embodiments, R² is C₂₋₃₀ alkyl substituted with one to fiveR¹⁹. In certain embodiments, R² is C₂₋₃₀ heteroalkyl substituted withone to five R¹⁹. In certain embodiments, R² is —O(CH₂)_(m)CH₃ or—O(CH₂)_(m)CH₂C(O)OH, wherein m is an integer selected from 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, and 29.

In certain embodiments, R² is —OR¹⁸, wherein R¹⁸ is C₄₋₃₀ alkyloptionally substituted with one to five R¹⁹.

In certain embodiments, R² is —NO₂. In certain embodiments, R² is —CN.

In certain embodiments, R² is —OR¹⁸ or —S(O)₀₋₂R¹⁸. In certainembodiments, R¹⁸ is C₁₋₃₀ haloalkyl. In certain embodiments, R¹⁸ isC₂₋₃₀ alkyl optionally substituted with one to five R¹⁹. In certainembodiments, R¹⁸ is C₁₋₃₀ heteroalkyl optionally substituted with one tofive R¹⁹.

In certain embodiments, each R¹⁹ is independently selected from halo,—NH₂, —OH, —CN, —NO₂, oxo, C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂,—C(O)—C₁₋₄ alkyl, and —C(O)OH. In certain embodiments, R¹⁹ is —C(O)OH.

In certain embodiments, R² is C₁₋₃₀ alkyl, —CN, —NO₂ and —OR¹⁸. Incertain embodiments, R² is —CH₃, —CH₂CH₃, —NO₂, —OCF₃, and —OR¹⁸. Incertain embodiments, R² is —OR¹⁸, wherein R¹⁸ is C₄₋₃₀ alkyl optionallysubstituted with one to five R¹⁹.

In certain embodiments, R⁶ is selected from C₁₋₆ alkyl substituted withone to five R²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —NO₂,—NR¹⁵R¹⁵, —C(O)NR¹⁵R¹⁵, —S(O)₀₋₂NHR¹⁶, —NHS(O)₀₋₂R¹⁶, heterocyclyloptionally substituted with one to five R²⁹, heteroaryl optionallysubstituted with one to five R³⁰, poly(ethylene glycol), andmethoxypoly(ethylene glycol), wherein R¹⁷ is selected from C₁₋₃₀ alkylsubstituted with one to five R²⁷, C₁₋₃₀ heteroalkyl optionallysubstituted with one to five R²⁷, C₃₋₁₀ cycloalkyl optionallysubstituted with one to five R²⁷, heterocyclyl optionally substitutedwith one to five R²⁷, aryl optionally substituted with one to five R²⁴,heteroaryl optionally substituted with one to five R²⁴, poly(ethyleneglycol), and methoxypoly(ethylene glycol).

In certain embodiments, R⁶ is —NO₂, —C(O)OR¹⁵, —OC(O)R¹⁶, —C(O)NR¹⁵R¹⁵,—NR¹⁵C(O)R¹⁵, —S(O)₀₋₂R¹⁶, —S(O)₀₋₂NHR¹⁶, or —NHS(O)₀₋₂R¹⁶.

In certain embodiments, R⁶ is a sugar moiety.

In certain embodiments, R⁶ is halo, C₁₋₃₀ alkyl optionally substitutedwith one to five R²⁹, C₁₋₃₀ heteroalkyl optionally substituted with oneto five R²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂,—NR¹⁵R¹⁵, —C(O)NR¹⁵R¹⁵, —NR¹⁵C(O)R¹⁶, S(O)₀₋₂NR¹⁵R¹⁵, —NR¹⁵S(O)₀₋₂R¹⁶,heterocyclyl optionally substituted with one to five R²⁹, heteroaryloptionally substituted with one to five R³⁰, poly(ethylene glycol), andmethoxypoly(ethylene glycol).

In certain embodiments, R⁶ is halo, OR¹⁷, or C₁₋₃₀ alkyl optionallysubstituted with halo or C(O)OH, wherein R¹⁷ is C₁₋₃₀ alkyl optionallysubstituted with halo or C(O)OH. In certain embodiments, R⁶ is F, C₁-C₄alkyl or C₁-C₄ alkoxy. In certain embodiments, R⁶ is OR¹⁷, and R¹⁷ isC₁-C₄ haloalkyl. In certain embodiments, R⁶ is selected from CH₂CN, OCF₃and NO₂.

In certain embodiments, R⁶ is S(O)₀₋₂R¹⁶. In certain embodiments, R¹⁶ isC₁-C₃₀ alkyl optionally substituted with halo or C(O)OH. In certainembodiments, R⁶ is SCH₃, SOCH₃, and SO₂CH₃. In certain embodiments, R⁶is C(O)OR¹⁵. In certain embodiments, R¹⁵ is H or C₁₋₃₀ alkyl optionallysubstituted with halo or C(O)OH. In certain embodiments, R⁶ is —C(O)OH,—C(O)OCH₃ or —C(O)OCH₂CH₃.

In certain embodiments, R⁶ is —C(O)NR¹⁵R¹⁵. In certain embodiments, oneR¹⁵ is H or alkyl. In certain embodiments, one R¹⁵ is H, C₁₋₃₀ alkyloptionally substituted with one to five R²³, C₁₋₃₀ heteroalkyloptionally substituted with one to five R²⁰, and heterocyclyl optionallysubstituted with one to five R²³.

In certain embodiments, one R¹⁵ is a sugar moiety. In certainembodiments, one R¹⁶ is a sugar moiety.

In certain embodiments, R⁶ is a sugar moiety.

In certain embodiments, R⁶ is selected from

In certain embodiments, R⁶ and R⁷ together with atoms to which they areattached form C₅₋₁₀ cycloalkyl optionally substituted with one to fiveR²⁹. In certain embodiments, R⁶ and IV together with atoms to which theyare attached form heterocyclyl optionally substituted with one to fiveR²⁹. In certain embodiments, R⁶ and IV together with atoms to which theyare attached form aryl optionally substituted with one to five R³⁰. Incertain embodiments, R⁶ and R⁷ together with atoms to which they areattached form heteroaryl optionally substituted with one to five R³⁰. Incertain embodiments, one R²⁹ is a sugar moiety. In certain embodiments,one R³⁰ is a sugar moiety.

In certain embodiments, R⁵, R⁷ and R⁸ are each H. In certainembodiments, R⁵ and R⁸ are each H, and R⁷ is OCH₃.

In certain embodiments, R¹, R⁶ and R² are each not H. In certainembodiments, R¹, R⁶, R¹, and R² are each not H.

In certain embodiments, R² is —OR¹⁸, wherein R¹⁸ is C₄₋₃₀ alkyloptionally substituted with one to five R¹⁹; R⁶ is —NO₂, —C(O)OR¹⁵,—OC(O)R¹⁶, —C(O)NR¹⁵R¹⁵, —NR¹⁵C(O)R¹⁵, —S(O)₀₋₂R¹⁶, —S(O)₀₋₂NHR¹⁶, or—NHS(O)₀₋₂R¹⁶; R⁵, R⁷ and R⁸ are each H, or R⁵ and R⁸ are each H, and R⁷is OCH₃.

In certain embodiments, the compound has no more than one group selectedfrom poly(ethylene glycol), methoxypoly(ethylene glycol) and sugarmoiety.

Provided herein is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   R¹ is selected from —NR³R⁴, heterocyclyl optionally substituted        with one to five R²⁰, and heteroaryl optionally substituted with        one to five R²¹;    -   R² is selected from H, halo, C₁₋₃₀ alkyl optionally substituted        with one to five R¹⁹, C₁₋₃₀ heteroalkyl optionally substituted        with one to five R¹⁹, —OH, —OR¹⁸, —CN, —NO₂, —NH₂, —S(O)₀₋₂R¹⁸,        and —NR¹¹R¹⁸;    -   R³ is selected from H, C₁₋₆ alkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹, and        heteroaryl optionally substituted with one to five R²¹,    -   R⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹,        heteroaryl optionally substituted with one to five R²¹,        poly(ethylene glycol), methoxypoly(ethylene glycol), and        —NR¹³R¹⁴;    -   R⁵, R⁷ and R⁸ are each independently selected from H, halo,        C₁₋₃₀ alkyl optionally substituted with one to five R²⁹, C₁₋₃₀        heteroalkyl optionally substituted with one to five R²⁹, —OR¹⁵,        —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂, —NR¹⁵R¹⁵, and        —C(O)NR¹⁵R¹⁵;    -   R⁶ is selected from H, halo, C₁₋₃₀ alkyl optionally substituted        with one to five R²⁹, C₁₋₃₀ heteroalkyl optionally substituted        with one to five R²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶,        —CN, —NO₂, —NR¹⁵R¹⁵, —C(O)NR¹⁵R¹⁵, —NR¹⁵C(O)R¹⁶,        —S(O)₀₋₂NR¹⁵R¹⁵, —NR¹⁵S(O)₀₋₂R¹⁶, heterocyclyl optionally        substituted with one to five R²⁹, heteroaryl optionally        substituted with one to five R³⁰, poly(ethylene glycol), and        methoxypoly(ethylene glycol), or    -   R⁶ and R⁷ together with atoms to which they are attached form        C₅₋₁₀ cycloalkyl optionally substituted with one to five R²⁹,        heterocyclyl optionally substituted with one to five R²⁹, aryl        optionally substituted with one to five R³⁰, or heteroaryl        optionally substituted with one to five R³⁰;    -   R⁹ is independently selected from halo, C₁₋₈alkyl optionally        substituted with one to five R²², —OH, —CN, and —NR¹¹R¹²;    -   n is 0, 1, 2, 3 or 4;    -   R¹⁰ is independently selected from C₁₋₁₀ alkyl optionally        substituted with one to five R²², and C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²²;    -   R¹¹ and R¹² are each independently H or C₁₋₆ alkyl optionally        substituted with one to five R²²;    -   R¹³ is selected from H, C₁₋₆ alkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹, and        heteroaryl optionally substituted with one to five R²¹;    -   R¹⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹,        heteroaryl optionally substituted with one to five R²¹,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   each R¹⁵ is independently selected from H, C₁₋₃₀ alkyl        optionally substituted with one to five R²³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R²³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²³, heterocyclyl        optionally substituted with one to five R²³, aryl optionally        substituted with one to five R²⁴, heteroaryl optionally        substituted with one to five R²⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   R¹⁶ is selected from C₁₋₃₀ alkyl optionally substituted with one        to five R²³, C₁₋₃₀ heteroalkyl optionally substituted with one        to five R²³, C₃₋₁₀ cycloalkyl optionally substituted with one to        five R²³, heterocyclyl optionally substituted with one to five        R²³, aryl optionally substituted with one to five R²⁴,        heteroaryl optionally substituted with one to five R²⁴,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   R¹⁷ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁷, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁷, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁷, heterocyclyl optionally substituted with one to        five R²⁷, aryl optionally substituted with one to five R²⁴,        heteroaryl optionally substituted with one to five R²⁴,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   R¹⁸ is selected from C₁₋₃₀ alkyl optionally substituted with one        to five R¹⁹ and C₁₋₃₀ heteroalkyl optionally substituted with        one to five R¹⁹;    -   each R²⁰ is independently selected from halo, oxo, —NH₂, —OH,        —CN, —NO₂, —OR²⁸, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸,        —C(O)OH, —OC(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,        —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂, —C(O)NHR²⁸, —C(O)N(R²⁸)₂, —NHC(O)R²⁸,        —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂,        —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);    -   each R²¹ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, —OR²⁸, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH,        —OC(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,        —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸, —C(O)N(R²⁸)₂,        —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂,        —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₆ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);    -   each R¹⁹ or R²² is independently selected from halo, —NH₂, —OH,        —CN, —NO₂, oxo, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl,        C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl,        —C(O)O—C₁₋₄ alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄        alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl,        —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,        —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂,        —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, and C₃₋₁₀ cycloalkyl;    -   each R²⁵ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, oxo, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH,        —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R³³, heterocyclyl        optionally substituted with one to five R³³, aryl optionally        substituted with one to five R³⁴, heteroaryl optionally        substituted with one to five R³⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   each R²⁶ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH,        —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R³³, heterocyclyl        optionally substituted with one to five R³³, aryl optionally        substituted with one to five R³⁴, heteroaryl optionally        substituted with one to five R³⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   each R³¹ is independently selected C₁₋₃₀ alkyl optionally        substituted with one to five R³³, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R³³, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R³³, heterocyclyl optionally        substituted with one to five R³³, aryl optionally substituted        with one to five R³⁴, heteroaryl optionally substituted with one        to five R³⁴, poly(ethylene glycol) and methoxypoly(ethylene        glycol);    -   each R³² is independently selected H and C₁₋₄ alkyl;    -   each R²³, R²⁷, R²⁹ or R³³ is independently selected from halo,        —NH₂, —OH, —CN, —NO₂, oxo, C₁₋₄ alkyl optionally substituted        with phenyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy,        —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)O—C₁₋₄        alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl,        —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl, —C(O)NH—C₁₋₄        alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂, —OC(O)NH—C₁₋₄        alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄        haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl        heteroaryl, —(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene        glycol), methoxypoly(ethylene glycol)-O—(CH₂)₀₋₄—, and sugar        moiety;    -   each R²⁴, R³⁰ or R³⁴ is independently selected from halo, —NH₂,        —OH, —CN, —NO₂, C₁₋₄ alkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ haloalkyl,        C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl,        —C(O)OH, —C(O)O—C₁₋₄ alkyl, —S(O)₀₋₂—C₁₋₄ alkyl,        —NHS(O)₀₋₂—C₁₋₄₀ alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄        alkyl, —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄        alkyl)₂, —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄        alkyl)₂, —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄        haloalkyl, —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl,        heteroaryl, —(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene        glycol), —(CH₂)₀₋₄—O-methoxypoly(ethylene glycol) and sugar        moiety; and    -   each R²⁸ is independently selected from C₁₋₃₀ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);        provided at least that the compound has at least one of the        following:    -   (1) R² is selected from C₂₋₃₀ alkyl optionally substituted with        one to five R¹⁹, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R¹⁹, —NO₂, —OR¹⁸, —S(O)₀₋₂R¹⁸, and —NR¹¹R¹⁸, wherein        R¹⁸ is selected from C₁₋₃₀ haloalkyl, C₂₋₃₀ alkyl optionally        substituted with one to five R¹⁹ and C₂₋₃₀ heteroalkyl        optionally substituted with one to five R¹⁹; wherein when R² is        ethyl, then R⁶ is not methyl or methoxy;    -   (2) R¹ is heteroaryl optionally substituted with one to five        R²¹, or fused heterocyclyl optionally substituted with one to        five R²⁰;    -   (3) R¹ is heterocyclyl substituted with at least one R²⁰        selected from halo, oxo, —NH₂, —OH, —CN, —NO₂, —NHR²⁸, —N(R²⁸)₂,        —C(O)R²⁸, —C(O)OR^(28a), —NHS(O)₀₋₂R²⁸, —OC(O)R²⁸, —S(O)₀₋₂R²⁸,        —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸,        —C(O)N(R²⁸)₂, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl substituted with        one to five R²⁵, heteroaryl optionally substituted with one to        five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);        -   wherein            -   the C₁₋₃₀ alkyl is substituted with at least one R²⁵                selected from halo, —NH₂, —OH, —CN, —NO₂, oxo, —NHR³¹,                —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH, —S(O)₀₋₂R³¹,                —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹, —NR³²S(O)₀₋₂NR³²R³¹,                —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹, —C(O)N(R³¹)₂,                —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂, —NR³²C(O)NH₂,                —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl optionally                substituted with one to five R³³, C₁₋₃₀ heteroalkyl                optionally substituted with one to five R³³,                heterocyclyl substituted with one to five R³³,                poly(ethylene glycol), methoxypoly(ethylene glycol),                pyrrolidinyl and piperidinyl; or the C₁₋₃₀ alkyl is                substituted with at least one —OR³¹, wherein R³¹ is                poly(ethylene glycol) or methoxypoly(ethylene glycol);            -   R^(28a) is selected from C₁₋₃₀ alkyl substituted with                one to five R²⁵, C₁₋₃₀ heteroalkyl optionally                substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl                optionally substituted with one to five R²⁵,                heterocyclyl optionally substituted with one to five                R²⁵, aryl optionally substituted with one to five R²⁶,                heteroaryl optionally substituted with one to five R²⁶,                poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   (4) R¹ is —NR³R⁴, and R⁴ is selected from C₁₋₃₀ alkyl        substituted with one to five R²⁰, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁰, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁰, heterocyclyl optionally        substituted with one to five R²⁰, heteroaryl optionally        substituted with one to five R²¹, poly(ethylene glycol),        methoxypoly(ethylene glycol), and —NR¹³R¹⁴;        -   wherein            -   the C₁₋₃₀ alkyl is substituted with at least one R²⁰                selected from halo, —NH₂, —OH, —CN, —NO₂, —NHR²⁸,                —N(R²⁸)₂, —C(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸,                —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸,                —C(O)N(R²⁸)₂, —OC(O)NHR²⁸, NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,                C₃₋₁₀ cycloalkyl optionally substituted with one to five                R²⁵, heterocyclyl optionally substituted with one to                five R²⁵, and heteroaryl optionally substituted with one                to five R²⁶; or    -   (5) R⁶ is selected from C₁₋₆ alkyl substituted with one to five        R²⁹, —OR¹⁷, —S(O)₀₋₂₈ ¹⁶, C(O)OR¹⁵, —OC(O)R¹⁶, —NO₂, —NR¹⁵R¹⁵,        —C(O)NR¹⁵R¹⁵, —S(O)₀₋₂NHR¹⁶, —NHS(O)₀₋₂₈ ¹⁶, heterocyclyl        optionally substituted with one to five _(R29), heteroaryl        optionally substituted with one to five R³⁰, poly(ethylene        glycol), and methoxypoly(ethylene glycol), wherein R¹⁷ is        selected from C₁₋₃₀ alkyl substituted with one to five R²⁷,        C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁷,        C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁷,        heterocyclyl optionally substituted with one to five R²⁷, aryl        optionally substituted with one to five R²⁴, heteroaryl        optionally substituted with one to five R²⁴, poly(ethylene        glycol), and methoxypoly(ethylene glycol).

Provided herein is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   R¹ is selected from —NR³R⁴, heterocyclyl optionally substituted        with one to five R²⁰, and heteroaryl optionally substituted with        one to five R²¹;    -   R² is selected from C₂₋₃₀ alkyl optionally substituted with one        to five R¹⁹, C₁₋₃₀ heteroalkyl optionally substituted with one        to five R¹⁹, —NO₂, —OR¹⁸, —S(O)₀₋₂R¹⁸, and —NR¹¹R¹⁸, wherein R¹⁸        is selected from C₁₋₃₀ haloalkyl, C₂₋₃₀ alkyl optionally        substituted with one to five R¹⁹ and C₂₋₃₀ heteroalkyl        optionally substituted with one to five R¹⁹; wherein when R² is        ethyl, then R⁶ is not methyl or methoxy;    -   R³ is selected from H, C₁₋₆ alkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹, and        heteroaryl optionally substituted with one to five R²¹;    -   R⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹,        heteroaryl optionally substituted with one to five R²¹,        poly(ethylene glycol), methoxypoly(ethylene glycol), and        —NR¹³R¹⁴;    -   R⁵, R⁷ and R⁸ are each independently selected from H, halo,        C₁₋₃₀ alkyl optionally substituted with one to five R²⁹, C₁₋₃₀        heteroalkyl optionally substituted with one to five R²⁹, —OR¹⁵,        —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂, —NR¹⁵R¹⁵, and        —C(O)NR¹⁵R¹⁵;    -   R⁶ is selected from H, halo, C₁₋₃₀ alkyl optionally substituted        with one to five R²⁹, C₁₋₃₀ heteroalkyl optionally substituted        with one to five R²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶,        —CN, —NO₂, —NR¹⁵R¹⁵, —C(O)NR¹⁵R¹⁵, —NR¹⁵C(O)R¹⁶,        —S(O)₀₋₂NR¹⁵R¹⁵, —NR¹⁵S(O)₀₋₂R¹⁶, heterocyclyl optionally        substituted with one to five R²⁹, heteroaryl optionally        substituted with one to five R³⁰, poly(ethylene glycol), and        methoxypoly(ethylene glycol), or    -   R⁶ and R⁷ together with atoms to which they are attached form        C₅₋₁₀ cycloalkyl optionally substituted with one to five R²⁹,        heterocyclyl optionally substituted with one to five R²⁹, aryl        optionally substituted with one to five R³⁰, or heteroaryl        optionally substituted with one to five R³⁰;    -   R⁹ is independently selected from halo, C₁₋₈ alkyl optionally        substituted with one to five R²², —OH, —OR¹⁰, —CN, and —NR¹¹R¹²;    -   n is 0, 1, 2, 3 or 4;    -   R¹⁰ is independently selected from C₁₋₁₀ alkyl optionally        substituted with one to five R²², and C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²²;    -   R¹¹ and R¹² are each independently H or C₁₋₆ alkyl optionally        substituted with one to five R²²;    -   R¹³ is selected from H, C₁₋₆ alkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹, and        heteroaryl optionally substituted with one to five R²¹;    -   R¹⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹,        heteroaryl optionally substituted with one to five R²¹,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   each R¹⁵ is independently selected from H, C₁₋₃₀ alkyl        optionally substituted with one to five R²³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R²³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²³, heterocyclyl        optionally substituted with one to five R²³, aryl optionally        substituted with one to five R²⁴, heteroaryl optionally        substituted with one to five R²⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   R¹⁶ is selected from C₁₋₃₀ alkyl optionally substituted with one        to five R²³, C₁₋₃₀ heteroalkyl optionally substituted with one        to five R²³, C₃₋₁₀ cycloalkyl optionally substituted with one to        five R²³, heterocyclyl optionally substituted with one to five        R²³, aryl optionally substituted with one to five R²⁴,        heteroaryl optionally substituted with one to five R²⁴,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   R¹⁷ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁷, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁷, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁷, heterocyclyl optionally substituted with one to        five R²⁷, aryl optionally substituted with one to five R²⁴,        heteroaryl optionally substituted with one to five R²⁴,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   R¹⁸ is selected from C₁₋₃₀ alkyl optionally substituted with one        to five R¹⁹ and C₁₋₃₀ heteroalkyl optionally substituted with        one to five R¹⁹;    -   each R²⁰ is independently selected from halo, oxo, —NH₂, —OH,        —CN, —NO₂, —OR²⁸, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸,        —C(O)OH, —OC(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,        —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂, —C(O)NHR²⁸, —C(O)N(R²⁸)₂, —NHC(O)R²⁸,        —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂,        —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);    -   each R²¹ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, —OR²⁸, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH,        —OC(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,        —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸, —C(O)N(R²⁸)₂,        —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂,        —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₆ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);    -   each R¹⁹ or R²² is independently selected from halo, —NH₂, —OH,        —CN, —NO₂, oxo, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl,        C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl,        —C(O)O—C₁₋₄ alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄        alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl,        —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,        —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂,        —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, and C₃₋₁₀ cycloalkyl;    -   each R²⁵ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, oxo, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH,        —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R³³, heterocyclyl        optionally substituted with one to five R³³, aryl optionally        substituted with one to five R³⁴, heteroaryl optionally        substituted with one to five R³⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   each R²⁶ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH,        —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R³³, heterocyclyl        optionally substituted with one to five R³³, aryl optionally        substituted with one to five R³⁴, heteroaryl optionally        substituted with one to five R³⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   each R³¹ is independently selected C₁₋₃₀ alkyl optionally        substituted with one to five R³³, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R³³, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R³³, heterocyclyl optionally        substituted with one to five R³³, aryl optionally substituted        with one to five R³⁴, heteroaryl optionally substituted with one        to five R³⁴, poly(ethylene glycol) and methoxypoly(ethylene        glycol);    -   each R³² is independently selected H and C₁₋₄ alkyl;    -   each R²³, R²⁷, R²⁹ or R³³ is independently selected from halo,        —NH₂, —OH, —CN, —NO₂, oxo, C₁₋₄ alkyl optionally substituted        with phenyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy,        —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)O—C₁₋₄        alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl,        —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl, —C(O)NH—C₁₋₄        alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂, —OC(O)NH—C₁₋₄        alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄        haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl        heteroaryl, —(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene        glycol), methoxypoly(ethylene glycol)-O—(CH₂)₀₋₄—, and sugar        moiety;    -   each R²⁴, R³⁰ or R³⁴ is independently selected from halo, —NH₂,        —OH, —CN, —NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl,        C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl,        —C(O)OH, —C(O)O—C₁₋₄ alkyl, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄        alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl,        —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,        —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂,        —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl,        heteroaryl, —(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene        glycol); —(CH₂)₀₋₄—O-methoxypoly(ethylene glycol) and sugar        moiety; and    -   each R²⁸ is independently selected from C₁₋₃₀ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol).

Provided herein is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   R¹ is heteroaryl optionally substituted with one to five R²¹, or        fused heterocyclyl optionally substituted with one to five R²⁰;        or    -   R¹ is heterocyclyl substituted with at least one R²⁰ selected        from halo, oxo, —NH₂, —OH, —CN, —NO₂, —OR²⁸, NHR²⁸, N(R²⁸)₂,        C(O)R²⁸, —C(O)OR^(28a), —NHS(O)₀₋₂R²⁸, —OC(O)R²⁸, —S(O)₀₋₂R²⁸,        —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸,        —C(O)N(R²⁸)₂, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, heterocyclyl substituted with        one to five R²⁵, poly(ethylene glycol), and methoxypoly(ethylene        glycol); wherein at least one R²⁵ is selected from halo, —NH₂,        —OH, —CN, —NO₂, oxo, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹,        —C(O)OH, —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, heterocyclyl        substituted with one to five R³³, poly(ethylene glycol),        methoxypoly(ethylene glycol), pyrrolidinyl and piperidinyl; or        the C₁₋₃₀ alkyl is substituted with at least one —OR^(31a),        wherein R^(31a) is poly(ethylene glycol) or methoxypoly(ethylene        glycol); and R^(28a) is selected from C₁₋₃₀ alkyl substituted        with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally substituted        with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally substituted        with one to five R²⁵, heterocyclyl optionally substituted with        one to five R²⁵, aryl optionally substituted with one to five        R²⁶, heteroaryl optionally substituted with one to five R²⁶,        poly(ethylene glycol), and methoxypoly(ethylene glycol); or    -   R¹ is —NR³R⁴,    -   R² is selected from H, halo, C₁₋₃₀ alkyl optionally substituted        with one to five R¹⁹, C₁₋₃₀ heteroalkyl optionally substituted        with one to five R¹⁹, —OH, —OR¹⁸, —CN, —NO₂, —NH₂, —S(O)₀₋₂R¹⁸,        and —NR¹¹R¹⁸;    -   R³ is selected from H, C₁₋₆ alkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹, and        heteroaryl optionally substituted with one to five R²¹, and    -   R⁴ is selected from C₁₋₃₀ alkyl substituted with one to five        R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with one to five        R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with one to five        R²⁰, heterocyclyl optionally substituted with one to five R²⁰,        heteroaryl optionally substituted with one to five R²¹,        poly(ethylene glycol), methoxypoly(ethylene glycol), and        —NR¹³R¹⁴, wherein the C₁₋₃₀ alkyl is substituted with at least        one R²⁰ selected from halo, —NH₂, —OH, —CN, —NO₂, —OR²⁸, —NHR²⁸,        —N(R²⁸)₂, —C(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,        —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸, C(O)N(R²⁸)₂,        OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²⁵, heterocyclyl        optionally substituted with one to five R²⁵, and heteroaryl        optionally substituted with one to five R²⁶;    -   R⁵, R⁷ and R⁸ are each independently selected from H, halo,        C₁₋₃₀ alkyl optionally substituted with one to five R²⁹, C₁₋₃₀        heteroalkyl optionally substituted with one to five R²⁹, —OR¹⁵,        —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂, —NR¹⁵R¹⁵, and        —C(O)NR¹⁵R¹⁵;    -   R⁶ is selected from H, halo, C₁₋₃₀ alkyl optionally substituted        with one to five R²⁹, C₁₋₃₀ heteroalkyl optionally substituted        with one to five R²⁹, —OR¹⁷, —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶,        —CN, —NO₂, —NR¹⁵R¹⁵, —C(O)NR¹⁵R¹⁵, —NR¹⁵C(O)R¹⁶,        —S(O)₀₋₂NR¹⁵R¹⁵, —NR¹⁵S(O)₀₋₂R¹⁶, heterocyclyl optionally        substituted with one to five R²⁹, heteroaryl optionally        substituted with one to five R³⁰, poly(ethylene glycol),        methoxypoly(ethylene glycol), and sugar moiety, or R⁶ and IV        together with atoms to which they are attached form C₅₋₁₀        cycloalkyl optionally substituted with one to five R²⁹,        heterocyclyl optionally substituted with one to five R²⁹, aryl        optionally substituted with one to five R³⁰, or heteroaryl        optionally substituted with one to five R³⁰;    -   R⁹ is independently selected from halo, C₁₋₈ alkyl optionally        substituted with one to five R²², —OH, —CN, and —NR¹¹R¹²;    -   n is 0, 1, 2, 3 or 4;    -   R¹⁰ is independently selected from C₁₋₁₀ alkyl optionally        substituted with one to five R²², and C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²²;    -   R¹¹ and R¹² are each independently H or C₁₋₆ alkyl optionally        substituted with one to five R²²;    -   R¹³ is selected from H, C₁₋₆ alkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹, and        heteroaryl optionally substituted with one to five R²¹;    -   R¹⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹,        heteroaryl optionally substituted with one to five R²¹,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   each R¹⁵ is independently selected from H, C₁₋₃₀ alkyl        optionally substituted with one to five R²³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R²³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²³, and heterocyclyl        optionally substituted with one to five R²³, aryl optionally        substituted with one to five R²⁴, heteroaryl optionally        substituted with one to five R²⁴, poly(ethylene glycol),        methoxypoly(ethylene glycol);    -   R¹⁶ is selected from C₁₋₃₀ alkyl optionally substituted with one        to five R²³, C₁₋₃₀ heteroalkyl optionally substituted with one        to five R²³, C₃₋₁₀ cycloalkyl optionally substituted with one to        five R²³, heterocyclyl optionally substituted with one to five        R²³, aryl optionally substituted with one to five R²⁴,        heteroaryl optionally substituted with one to five R²⁴,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   R¹⁷ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁷, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁷, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁷, heterocyclyl optionally substituted with one to        five R²⁷, aryl optionally substituted with one to five R²⁴,        heteroaryl optionally substituted with one to five R²⁴,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   R¹⁸ is selected from C₁₋₃₀ alkyl optionally substituted with one        to five R¹⁹ and C₁₋₃₀ heteroalkyl optionally substituted with        one to five R¹⁹;    -   each R²⁰ is independently selected from halo, oxo, —NH₂, —OH,        —CN, —NO₂, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, C(O)R²⁸, —C(O)OR²⁸,        —C(O)OH, —OC(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,        —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂, —C(O)NHR²⁸, —C(O)N(R²⁸)₂, —NHC(O)R²⁸,        —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂,        —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);    -   each R²¹ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH, —OC(O)R²⁸,        —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸,        —C(O)NHR²⁸, —NHC(O)R²⁸, —C(O)N(R²⁸)₂, OC(O)NHR²⁸, —NHC(O)OR²⁸,        —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂, —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂,        C₁₋₆ alkyl optionally substituted with one to five R²⁵, C₁₋₃₀        heteroalkyl optionally substituted with one to five R²⁵, C₃₋₁₀        cycloalkyl optionally substituted with one to five R²⁵,        heterocyclyl optionally substituted with one to five R²⁵, aryl        optionally substituted with one to five R²⁶, heteroaryl        optionally substituted with one to five R²⁶, poly(ethylene        glycol), and methoxypoly(ethylene glycol);    -   each R¹⁹ or R²² is independently selected from halo, —NH₂, —OH,        —CN, —NO₂, oxo, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl,        C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl,        —C(O)O—C₁₋₄ alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄        alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl,        —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,        —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂,        —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, and C₃₋₁₀ cycloalkyl;    -   each R²⁵ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, oxo, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH,        —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R³³, heterocyclyl        optionally substituted with one to five R³³, aryl optionally        substituted with one to five R³⁴, heteroaryl optionally        substituted with one to five R³⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   each R²⁶ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH,        —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R³³, heterocyclyl        optionally substituted with one to five R³³, aryl optionally        substituted with one to five R³⁴, heteroaryl optionally        substituted with one to five R³⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   each R³¹ is independently selected C₁₋₃₀ alkyl optionally        substituted with one to five R³³, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R³³, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R³³, heterocyclyl optionally        substituted with one to five R³³, aryl optionally substituted        with one to five R³⁴, heteroaryl optionally substituted with one        to five R³⁴, poly(ethylene glycol) and methoxypoly(ethylene        glycol);    -   each R³² is independently selected H and C₁₋₄ alkyl;    -   each R²³, R²⁷, R²⁹ or R³³ is independently selected from halo,        —NH₂, —OH, —CN, —NO₂, oxo, C₁₋₄ alkyl optionally substituted        with phenyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy,        —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)O—C₁₋₄        alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl,        —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂ NH—C₁₋₄ alkyl, —C(O)NH—C₁₋₄        alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂, —OC(O)NH—C₁₋₄        alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄        haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl        heteroaryl, —(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene        glycol), methoxypoly(ethylene glycol)-O—(CH₂)₀₋₄—, and sugar        moiety;    -   each R²⁴, R³⁰ or R³⁴ is independently selected from halo, —NH₂,        —OH, —CN, —NO₂, C₁₋₄ alkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ haloalkyl,        C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl,        —C(O)OH, —C(O)O—C₁₋₄ alkyl, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄        alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl,        —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,        —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂,        —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl,        heteroaryl, —(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene        glycol), —(CH₂)₀₋₄—O-methoxypoly(ethylene glycol) and sugar        moiety; and    -   each R²⁸ is independently selected from C₁₋₃₀ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol).

Provided herein is a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein

-   -   R¹ is selected from —NR³R⁴, heterocyclyl optionally substituted        with one to five R²⁰, and heteroaryl optionally substituted with        one to five R²¹;    -   R² is selected from H, halo, C₁₋₃₀ alkyl optionally substituted        with one to five R¹⁹, C₁₋₃₀ heteroalkyl optionally substituted        with one to five R¹⁹, —OH, —OR¹⁸, —CN, —NO₂, —NH₂, —S(O)₀₋₂R¹⁸,        and —NR¹¹R¹⁸;    -   R³ is selected from H, C₁₋₆ alkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹, and        heteroaryl optionally substituted with one to five R²¹,    -   R⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹,        heteroaryl optionally substituted with one to five R²¹,        poly(ethylene glycol), methoxypoly(ethylene glycol), and        —NR¹³R¹⁴;    -   R⁵, R⁷ and R⁸ are each independently selected from H, halo,        C₁₋₃₀ alkyl optionally substituted with one to five R²⁹, C₁₋₃₀        heteroalkyl optionally substituted with one to five R²⁹, —OR¹⁵,        —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —OC(O)R¹⁶, —CN, —NO₂, —NR¹⁵R¹⁵, and        —C(O)NR¹⁵R¹⁵;    -   R⁶ is selected from C₁₋₆ alkyl substituted with one to five R²⁹,        —OR¹⁷, —S(O)₀₋₂R¹⁶, C(O)OR¹⁵, —OC(O)R¹⁶, —NO₂, —NR¹⁵R¹⁵,        —C(O)NR¹⁵R¹⁵, —S(O)₀₋₂NHR¹⁶, —NHS(O)₀₋₂R¹⁶, heterocyclyl        optionally substituted with one to five R²⁹, heteroaryl        optionally substituted with one to five R³⁰, poly(ethylene        glycol), and methoxypoly(ethylene glycol), wherein R¹⁷ is        selected from C₁₋₃₀ alkyl substituted with one to five R²⁷,        C₁₋₃₀ heteroalkyl optionally substituted with one to five R²⁷,        C₃₋₁₀ cycloalkyl optionally substituted with one to five R²⁷,        heterocyclyl optionally substituted with one to five R²⁷, aryl        optionally substituted with one to five R²⁴, heteroaryl        optionally substituted with one to five R²⁴, poly(ethylene        glycol), and methoxypoly(ethylene glycol);    -   R⁹ is independently selected from halo, C₁₋₈ alkyl optionally        substituted with one to five R²², —OH, —OR¹⁰, —CN, and —NR¹¹R¹²;    -   n is 0, 1, 2, 3 or 4;    -   R¹⁰ is independently selected from C₁₋₁₀ alkyl optionally        substituted with one to five R²², and C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²²;    -   R¹¹ and R¹² are each independently H or C₁₋₆ alkyl optionally        substituted with one to five R²²;    -   R¹³ is selected from H, C₁₋₆ alkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹, and        heteroaryl optionally substituted with one to five R²¹;    -   R¹⁴ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁰, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁰, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁰, heterocyclyl optionally substituted with one to        five R²⁰, aryl optionally substituted with one to five R²¹,        heteroaryl optionally substituted with one to five R²¹,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   each R¹⁵ is independently selected from H, C₁₋₃₀ alkyl        optionally substituted with one to five R²³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R²³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R²³, heterocyclyl        optionally substituted with one to five R²³, aryl optionally        substituted with one to five R²⁴, heteroaryl optionally        substituted with one to five R²⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   R¹⁶ is selected from C₁₋₃₀ alkyl optionally substituted with one        to five R²³, C₁₋₃₀ heteroalkyl optionally substituted with one        to five R²³, C₃₋₁₀ cycloalkyl optionally substituted with one to        five R²³, heterocyclyl optionally substituted with one to five        R²³, aryl optionally substituted with one to five R²⁴,        heteroaryl optionally substituted with one to five R²⁴,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   R¹⁷ is selected from H, C₁₋₃₀ alkyl optionally substituted with        one to five R²⁷, C₁₋₃₀ heteroalkyl optionally substituted with        one to five R²⁷, C₃₋₁₀ cycloalkyl optionally substituted with        one to five R²⁷, heterocyclyl optionally substituted with one to        five R²⁷, aryl optionally substituted with one to five R²⁴,        heteroaryl optionally substituted with one to five R²⁴,        poly(ethylene glycol), and methoxypoly(ethylene glycol);    -   R¹⁸ is selected from C₁₋₃₀ alkyl optionally substituted with one        to five R¹⁹ and C₁₋₃₀ heteroalkyl optionally substituted with        one to five R¹⁹;    -   each R²⁰ is independently selected from halo, oxo, —NH₂, —OH,        —CN, —NO₂, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH,        —OC(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,        —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂, —C(O)NHR²⁸, —C(O)N(R²⁸)₂, —NHC(O)R²⁸,        —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂,        —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₃₀ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);    -   each R²¹ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, —OR²⁸, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸, —C(O)OR²⁸, —C(O)OH,        —OC(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸, —S(O)₀₋₂NHR²⁸,        —NHS(O)₀₋₂NHR²⁸, —C(O)NHR²⁸, —NHC(O)R²⁸, —C(O)N(R²⁸)₂,        —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂,        —NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, C₁₋₆ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃ to cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol);    -   each R²² is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, oxo, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄        alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl,        —C(O)O—C₁₋₄ alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄        alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl,        —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,        —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂,        —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, and C₃₋₁₀ cycloalkyl;    -   each R²⁵ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, oxo, —OR³¹, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹,        —C(O)OH, —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R³³, heterocyclyl        optionally substituted with one to five R³³, aryl optionally        substituted with one to five R³⁴, heteroaryl optionally        substituted with one to five R³⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   each R²⁶ is independently selected from halo, —NH₂, —OH, —CN,        —NO₂, —OR³¹, —NHR³¹, —N(R³¹)₂, —C(O)R³¹, —C(O)OR³¹, —C(O)OH,        —S(O)₀₋₂R³¹, —NR³²S(O)₀₋₂R³¹, —S(O)₀₋₂NR³²R³¹,        —NR³²S(O)₀₋₂NR³²R³¹, —C(O)NH₂, —C(O)NHR³¹, —NR³²C(O)R³¹,        —C(O)N(R³¹)₂, —OC(O)NHR³¹, —NR³²C(O)OR³¹, —OC(O)N(R³¹)₂,        —NR³²C(O)NH₂, —NR³²C(O)NHR³¹, —NR³²C(O)N(R³¹)₂, C₁₋₃₀ alkyl        optionally substituted with one to five R³³, C₁₋₃₀ heteroalkyl        optionally substituted with one to five R³³, C₃₋₁₀ cycloalkyl        optionally substituted with one to five R³³, heterocyclyl        optionally substituted with one to five R³³, aryl optionally        substituted with one to five R³⁴, heteroaryl optionally        substituted with one to five R³⁴, poly(ethylene glycol), and        methoxypoly(ethylene glycol);    -   each R³¹ is independently selected C₁₋₃₀ alkyl optionally        substituted with one to five R³³, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R³³, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R³³, heterocyclyl optionally        substituted with one to five R³³, aryl optionally substituted        with one to five R³⁴, heteroaryl optionally substituted with one        to five R³⁴, poly(ethylene glycol) and methoxypoly(ethylene        glycol);    -   each R³² is independently selected H and C₁₋₄ alkyl;    -   each R²³, R²⁷, R²⁹ or R³³ is independently selected from halo,        —NH₂, —OH, —CN, —NO₂, oxo, C₁₋₄ alkyl optionally substituted        with phenyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy,        —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl, —C(O)O—C₁₋₄        alkyl, —C(O)OH, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄ alkyl,        —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl, —C(O)NH—C₁₋₄        alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂, —OC(O)NH—C₁₋₄        alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂, —NH—C₁₋₄        haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl        heteroaryl, (CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene glycol),        methoxypoly(ethylene glycol)-O—(CH₂)₀₋₄—, and sugar moiety;    -   each R²⁴, R³⁰ or R³⁴ is independently selected from halo, —NH₂,        —OH, —CN, —NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ hydroxyalkyl,        C₁₋₄ alkoxy, —NH—C₁₋₄ alkyl, —N(C₁₋₄ alkyl)₂, —C(O)—C₁₋₄ alkyl,        —C(O)OH, —C(O)O—C₁₋₄ alkyl, —S(O)₀₋₂—C₁₋₄ alkyl, —NHS(O)₀₋₂—C₁₋₄        alkyl, —S(O)₀₋₂NH—C₁₋₄ alkyl, —NHS(O)₀₋₂NH—C₁₋₄ alkyl,        —C(O)NH—C₁₋₄ alkyl, —NHC(O)—C₁₋₄ alkyl, —C(O)N(C₁₋₄ alkyl)₂,        —OC(O)NH—C₁₋₄ alkyl, —NHC(O)O—C₁₋₄ alkyl, —OC(O)N(C₁₋₄ alkyl)₂,        —NH—C₁₋₄ haloalkyl, —N(C₁₋₄ haloalkyl)₂, —C(O)—C₁₋₄ haloalkyl,        —S(O)₀₋₂—C₁₋₄ haloalkyl, —NHS(O)₀₋₂—C₁₋₄ haloalkyl,        —S(O)₀₋₂NH—C₁₋₄ haloalkyl, —NHS(O)₀₋₂NH—C₁₋₄ haloalkyl,        —C(O)NH—C₁₋₄ haloalkyl, —NHC(O)—C₁₋₄ haloalkyl, —C(O)N(C₁₋₄        haloalkyl)₂, —OC(O)NH—C₁₋₄ haloalkyl, —NHC(O)O—C₁₋₄ haloalkyl,        —OC(O)N(C₁₋₄ haloalkyl)₂, C₃₋₁₀ cycloalkyl, heterocyclyl, aryl,        heteroaryl, —(CH₂)₁₋₃₀—C(O)OH, —(CH₂)₀₋₄—O-poly(ethylene        glycol), —(CH₂)₀₋₄—O-methoxypoly(ethylene glycol) and sugar        moiety; and    -   each R²⁸ is independently selected from C₁₋₃₀ alkyl optionally        substituted with one to five R²⁵, C₁₋₃₀ heteroalkyl optionally        substituted with one to five R²⁵, C₃₋₁₀ cycloalkyl optionally        substituted with one to five R²⁵, heterocyclyl optionally        substituted with one to five R²⁵, aryl optionally substituted        with one to five R²⁶, heteroaryl optionally substituted with one        to five R²⁶, poly(ethylene glycol), and methoxypoly(ethylene        glycol).

“Poly(ethylene glycol) refers to a polyether compound of general formula

where n varies from 2 to 500,000. In certain embodiments, poly(ethyleneglycol) has an average molecular weight of less than 20,000. In certainembodiments, poly(ethylene glycol) has an average molecular weight ofless than 15,000. In certain embodiments, poly(ethylene glycol) has anaverage molecular weight of less than 10,000. In certain embodiments,poly(ethylene glycol) has an average molecular weight of less than5,000. In certain embodiments, poly(ethylene glycol) has an averagemolecular weight of less than 2,000. In certain embodiments,poly(ethylene glycol) has an average molecular weight of about 20,000 toabout 2,000. In certain embodiments, poly(ethylene glycol) has anaverage molecular weight of about 10,000 to about 2,000.

“Methoxypoly(ethylene glycol) refers to a polyether compound of generalformula

where n varies from 2 to 500,000. In certain embodiments,methoxypoly(ethylene glycol) has an average molecular weight of lessthan 20,000. In certain embodiments, methoxypoly(ethylene glycol) has anaverage molecular weight of less than 15,000. In certain embodiments,methoxypoly(ethylene glycol) has an average molecular weight of lessthan 15,000. In certain embodiments, methoxypoly(ethylene glycol) has anaverage molecular weight of less than 10,000. In certain embodiments,methoxypoly(ethylene glycol) has an average molecular weight of lessthan 5,000. In certain embodiments, methoxypoly(ethylene glycol) has anaverage molecular weight of less than 2,000. In certain embodiments,methoxypoly(ethylene glycol) has an average molecular weight of about20,000 to about 2,000. In certain embodiments, methoxypoly(ethyleneglycol) has an average molecular weight of about 10,000 to about 2,000.

In some embodiments, provided is a compound of Formula (XII):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein:

-   -   R¹ is optionally substituted

-   -   each of s, t, u, v, p and q is independently 0, 1, 2, or 3,        provided that the sum of s and t is 1, 2, 3 or 4, the sum of u        and v is 1, 2, 3 or 4, and the sum of p and q is 1, 2, 3 or 4;    -   y is 0 or 1;    -   z is 0 or 1;    -   provided that y and z are not both 0;    -   Z¹ is C or N;    -   when Z¹ is C, R^(20a) is H, halo, hydroxy, alkyl, or        hydroxyalkyl;    -   when Z¹ is N, R^(20a) is absent;    -   Z² is CH or N;    -   Z³ is C or N;    -   when Z³ is C, R^(20b) is H, halo, hydroxy, alkyl, or        hydroxyalkyl;    -   when Z³ is N, R^(20b) is absent;    -   Z⁴ is CH or N;    -   Z⁵ is CH₂, CHR²⁵, CR²⁵R²⁵, C(═O), NR²⁵, O, or S(O)₀₋₂;    -   each R²⁵ is independently H, halo, alkyl or hydroxyalkyl;    -   R²¹¹ is C₂₋₄₀ alkyl, C₂₋₄₀ alkenyl, or C₂₋₄₀ alkynyl;    -   R⁶ is H, halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy,        alkylthio, sulfoxido, sulfonyl, carboxy, ester, —CN, —NO₂,        amino, amido, sulfinamido, or sulfonamido; and    -   R⁹¹ and R⁹² are independently selected from H and halo.

In some embodiments, provided is a pharmaceutical composition comprisinga compound of Formula (XII):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof;wherein:

-   -   R¹ is

-   -   each of s, t, u, v, p and q is independently 0, 1, 2, or 3,        provided that the sum of s and t is 1, 2, 3 or 4, the sum of u        and v is 1, 2, 3 or 4, and the sum of p and q is 1, 2, 3 or 4;    -   y is 0 or 1;    -   z is 0 or 1;    -   provided that y and z are not both 0;    -   Z¹ is CH or N;    -   Z² is CH or N;    -   Z³ is CH or N;    -   Z⁴ is CH or N;    -   Z⁵ is CH₂, CHR²⁵, CR²⁵R²⁵, C(═O), NR²⁵, O, or S(O)₀₋₂;    -   each R²⁵ is independently H, halo, alkyl or hydroxyalkyl;    -   R²¹¹ is C₂₋₄₀ alkyl, C₂₋₄₀ alkenyl, or C₂₋₄₀ alkynyl;    -   R⁶ is H, halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy,        alkylthio, sulfoxido, sulfonyl, carboxy, ester, —CN, —NO₂,        amino, amido, sulfinamido, or sulfonamido; and    -   R⁹¹ and R⁹² are independently selected from H and halo.

In some embodiments, in the compound of Formula (XII), R²¹¹ is C₅₋₄₀alkyl, C₅₋₄₀ alkenyl, or C₅₋₄₀ alkynyl. In some embodiments, in thecompound of Formula (XII), R²¹¹ is C₁₀₋₄₀ alkyl, C₁₀₋₄₀ alkenyl, orC₁₀₋₄₀ alkynyl. In some embodiments, in the compound of Formula (XII),R²¹¹ is C₁₀₋₂₅ alkyl, C₁₀₋₂₅ alkenyl, or C₁₀₋₂₅ alkynyl. In someembodiments, in the compound of Formula (XII), R²¹¹ is C₅₋₄₀ alkyl. Insome embodiments, in the compound of Formula (XII), R²¹¹ is C₁₀₋₄₀alkyl. In some embodiments, in the compound of Formula (XII), R²¹¹ isC₁₀₋₃₀ alkyl. In some embodiments, in the compound of Formula (XII),R²¹¹ is C₁₀₋₂₅ alkyl.

In some embodiments, in the compound of Formula (XII), R⁹¹ and R⁹² areindependently selected from H and F. In some embodiments, in thecompound of Formula (XII), R⁹¹ is H and R⁹² is F. In some embodiments,in the compound of Formula (XII), R⁹¹ is F and R⁹² is H. In someembodiments, in the compound of Formula (XII), R⁹¹ and R⁹² are both H.In some embodiments, in the compound of Formula (XII), R⁹¹ and R⁹² areboth F.

In some embodiments, in the compound of Formula (XII), R⁶ is hydroxy,alkoxy, haloalkoxy, alkylthio, sulfoxido, or sulfonyl. In someembodiments, in the compound of Formula (XII), R⁶ is hydroxy, or alkoxy.In some embodiments, in the compound of Formula (XII), R⁶ is alkylthio,sulfoxido, or sulfonyl. In some embodiments, in the compound of Formula(XII), R⁶ is sulfonyl. In some embodiments, in the compound of Formula(XII), R⁶ is sulfoxido. In some embodiments, in the compound of Formula(XII), R⁶ is methylsulfoxido.

In some embodiments, in the compound of Formula (XII), each ring in R¹is independently and optionally further substituted with halo, hydroxy,alkyl, hydroxyalkyl, or oxo. In some embodiments, in the compound ofFormula (XII), R¹ is

wherein Z¹, Z⁴, Z⁵, s, t, p, q and R^(20a) are as defined herein, andeach ring in R¹ is independently and optionally further substituted withhalo, hydroxy, alkyl, hydroxyalkyl, or oxo. In some embodiments, in thecompound of Formula (XII), R¹ is

wherein Z¹, Z², Z³, Z⁴, Z⁵, s, t, u, v, p, q, R^(20a) and R^(20b), areas defined herein, and each ring in R¹ is independently and optionallyfurther substituted with halo, hydroxy, alkyl, hydroxyalkyl, or oxo. Insome embodiments, in the compound of Formula (XII), R¹ is

wherein Z¹ is CH or N, and Z⁴, Z⁵, s, t, p, q are as defined herein. Insome embodiments, in the compound of Formula (XII), R¹ is

wherein Z¹ is CH or N, Z³ is CH or N, and Z², Z⁴, Z⁵, s, t, u, v, p, qare as defined herein.

In some embodiments, in the compound of Formula (XII), R¹ is selectedfrom

In some embodiments, in the compound of Formula (XII), R¹ is selectedfrom

In some embodiments, the compound of Formula (XII) is selected from

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof.

In some embodiments, any compound of Formula (I) or sub-formulaethereof, is a salt selected from mono, bis, or tris succinate, oxalate,citrate, maleate, adipate, or fumarate salts thereof. In someembodiments, any compound of Formula (I) or sub-formulae thereof, is ahydrate of a mono, bis or tris succinate, oxalate, citrate, maleate,adipate, or fumarate salt thereof, e.g., a salt of formula

In some embodiments, any compound of Formula (I) or sub-formulaethereof, is a mono, bis, or tris succinate salt. In some embodiments,any compound of Formula (I) or sub-formulae thereof, is a tris succinatesalt. In some embodiments, any compound of Formula (I) or sub-formulaethereof, is a tris succinate salt prepared from succinic acid dihydrate.

In some embodiments, any compound of Formula (I) or sub-formulaethereof, is a mono, bis, or tris oxalate salt. In some embodiments, anycompound of Formula (I) or sub-formulae thereof, is a tris oxalate salt.In some embodiments, any compound of Formula (I) or sub-formulaethereof, is a tris oxalate salt prepared from oxalic acid dihydrate.

In some embodiments, any compound of Formula (I) or sub-formulaethereof, is a mono, bis, or tris adipate salt. In some embodiments, anycompound of Formula (I) or sub-formulae thereof, is a tris adipate salt.In some embodiments, any compound of Formula (I) or sub-formulaethereof, is a tris adipate salt prepared from adipic acid dihydrate.

In certain embodiments, provided is a compound selected from Table 1, ora pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof.

TABLE 1 Ex. Structure Name 1

3-((4-ethylphenyl)sulfonyl)-4-(4- methylpiperazin-1-yl)-6-(trifluoromethoxy)quinoline 2

3-((4-ethylphenyl)sulfonyl)-4-(piperidin-1-yl)-6-(trifluoromethoxy)quinoline 3

4-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)morpholine 4

3-((4-ethylphenyl)sulfonyl)-4-(4- methylpiperidin-1-yl)-6-(trifluoromethoxy)quinoline 5

2-(4-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperazin-1-yl)ethan-1-ol 6

3-((4-ethylphenyl)sulfonyl)-4-(4- ethylpiperazin-1-yl)-6-(trifluoromethoxy)quinoline 7

3-((4-ethylphenyl)sulfonyl)-4-(4-methyl- 1,4-diazepan-1-yl)-6-(trifluoromethoxy)quinoline 8

1-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 9

ethyl 4-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperazine-1-carboxylate 10

3-((4-ethylphenyl)sulfonyl)-4-(4-(4- fluorophenyl)piperazin-1-yl)-6-(trifluoromethoxy)quinoline 11

4-([1,4′-bipiperidin]-1′-yl)-3-((4- ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 12

1-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)-4-phenylpiperidin-4-ol 13

3-((4-ethylphenyl)sulfonyl)-4-(4- phenylpiperazin-1-yl)-6-(trifluoromethoxy)quinoline 14

3-((4-ethylphenyl)sulfonyl)-4-(pyrrolidin-1-yl)-6-(trifluoromethoxy)quinoline 15

1-(3-((4-ethylphenyl)sulfonyl)-6- methoxyquinolin-4-yl)piperidin-4-ol 16

ethyl 4-(3-((4-ethylphenyl)sulfonyl)-6-methoxyquinolin-4-yl)piperazine-1- carboxylate 17

3-((4-ethylphenyl)sulfonyl)-4-(4-(4- fluorophenyl)piperazin-1-yl)-6-methoxyquinoline 18

N-cyclohexyl-3-((4- ethylphenyl)sulfonyl)-6- methoxyquinolin-4-amine 19

3-((4-ethylphenyl)sulfonyl)-N-(4- fluorophenyl)-6-methoxyquinolin-4-amine 20

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(4-methylpiperazin-1-yl)quinoline 21

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4- (piperidin-1-yl)quinoline 22

4-(3-((4-ethylphenyl)sulfonyl)-6- methoxyquinolin-4-yl)morpholine 23

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(4-methylpiperidin-1-yl)quinoline 24

3-((4-ethylphenyl)sulfonyl)-4-(4-ethylpiperazin-1-yl)-6-methoxyquinoline 25

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4- (pyrrolidin-1-yl)quinoline 26

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(4-phenylpiperazin-1-yl)quinoline 27

4-([1,4′-bipiperidin]-1′-yl)-3-((4- ethylphenyl)sulfonyl)-6-methoxyquinoline 28

1-(3-((4-ethylphenyl)sulfonyl)-6- methoxyquinolin-4-yl)-4-phenylpiperidin-4-ol 29

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(4-methyl-1,4-diazepan-1-yl)quinoline 30

3-((4-ethylphenyl)sulfonyl)-4-(4- isopropylpiperazin-1-yl)-6-methoxyquinoline 31

4-(azepan-1-yl)-3-((4- ethylphenyl)sulfonyl)-6- methoxyquinoline 32

3-((4-ethylphenyl)sulfonyl)-6-methyl-4-(4-methylpiperazin-1-yl)quinoline 33

3-((4-ethylphenyl)sulfonyl)-6-methyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline 34

1-(3-((4-ethylphenyl)sulfonyl)-6- methylquinolin-4-yl)piperidin-4-ol 35

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)-6-methylquinoline 36

3-((4-ethylphenyl)sulfonyl)-6-methyl-4- (piperidin-1-yl)quinoline 37

3-((4-ethylphenyl)sulfonyl)-6-fluoro-4-(4-methylpiperazin-1-yl)quinoline 38

3-((4-ethylphenyl)sulfonyl)-6-fluoro-4-(4-methyl-1,4-diazepan-1-yl)quinoline 39

1-(3-((4-ethylphenyl)sulfonyl)-6- fluoroquinolin-4-yl)piperidin-4-ol 40

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)-6-fluoroquinoline 41

3-((4-ethylphenyl)sulfonyl)-6-fluoro-4- (piperidin-1-yl)quinoline 42

2-(4-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-1,4- diazepan-1-yl)acetic acid 43

4-([1,4′-bipiperidin]-1′-yl)-3-((4- methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 44

1-(3-((4-methoxyphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 45

4-(4-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperazin-1-yl)benzonitrile 46

3-((4-ethylphenyl)sulfonyl)-4-(4- (pyrrolidin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 47

ethyl 1-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidine-4-carboxylate 48

(1-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidin-4-yl)methanol 49

N-benzyl-3-((4-ethylphenyl)sulfonyl)-N-methyl-6-(trifluoromethoxy)quinolin-4- amine 50

3-((4-ethylphenyl)sulfonyl)-N-(4- methylpiperazin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 51

3-((4-ethylphenyl)sulfonyl)-4-(1H-1,2,4- triazol-1-yl)-6-(trifluoromethoxy)quinoline 52

8-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane 53

1-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidine-4-carboxlic acid 54

4-((4-([1,4′-bipiperidin]-1′-yl)-6- (trifluoromethoxy)quinolin-3-yl)sulfonyl)benzonitrile 55

2-(4-([1,4′-bipiperidin]-1′-yl)-3-((4- ethylphenyl)sulfonyl)quinolin-6-yl)acetonitrile 56

4-([1,4′-bipiperidin]-1′-yl)-3-((3,4- dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 57

3-((3,4-dimethoxyphenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-6-(trifluoromethoxy)quinoline 58

1-(3-((3,4-dimethoxyphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 59

4-([1,4′-bipiperidin]-1′-yl)-3-((4- nitrophenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 60

4-(4-methyl-1,4-diazepan-1-yl)-3-((4- nitrophenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 61

1-(3-((4-nitrophenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 62

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4-hydroxypiperidin-1-yl)quinoline-6- carboxylate 63

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6- carboxylate 64

ethyl 4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6- carboxylate 65

3-((4-ethylphenyl)sulfonyl)-4-(4- hydroxypiperidin-1-yl)quinoline-6-carboxylic acid 66

3-((4-ethylphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxylic acid 67

4-([1,4′-bipiperidin]-1′-yl)-3-((4- ethylphenyl)sulfonyl)quinoline-6-carboxylic acid 68

3-((3,4-dimethoxyphenyl)sulfonyl)-N,N-diethyl-6-(trifluoromethoxy)quinolin-4- amine 69

2-((3-((3,4-dimethoxyphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)amino)ethan-1-ol 70

1-(3-((3,4-dimethoxyphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidin-3-ol 71

3-((3,4-dimethoxyphenyl)sulfonyl)-N,N-dipropyl-6-(trifluoromethoxy)quinolin-4- amine 72

2,2′-((3-((3,4-dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4- yl)azanediyl)bis(ethan-1-ol) 73

2-((3-((3,4-dimethoxyphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)amino)ethan-1-ol 74

N,N-dibutyl-3-((3,4- dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-amine 75

1-(3-((4-ethylphenyl)sulfonyl)-6- nitroquinolin-4-yl)piperidin-4-ol 76

3-((4-ethylphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-nitroquinoline 77

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)-6-nitroquinoline 78

N,N-diethyl-3-((4-ethylphenyl)sulfonyl)- 6-nitroquinolin-4-amine 79

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(1H-1,2,4-triazol-1-yl)quinoline 80

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinoline-6-carboxylate 81

N,N-diethyl-3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-amine 82

1-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)piperidin-3-ol 83

3-((4-ethylphenyl)sulfonyl)-6-methoxy-N-(4-methylpiperazin-1-yl)quinolin-4- amine 84

ethyl 3-((4-ethylphenyl)sulfonyl)-4-((4-methylpiperazin-1-yl)amino)quinoline-6- carboxylate 85

3-((4-methoxyphenyl)sulfonyl)-N-(4- methylpiperazin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 86

3-((4-methoxyphenyl)sulfonyl)-4-(1H- 1,2,4-triazol-1-yl)-6-(trifluoromethoxy)quinoline 87

N,N-dibutyl-3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-amine 88

3-((3,4-dimethoxyphenyl)sulfonyl)-N-(4- methylpiperazin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 89

3-((3,4-dimethoxyphenyl)sulfonyl)-4- (1H-1,2,4-triazol-1-yl)-6-(trifluoromethoxy)quinoline 90

N-(4-methylpiperazin-1-yl)-6- (trifluoromethoxy)-3-((4-(trifluoromethoxy)phenyl)sulfonyl)quinolin- 4-amine 91

4-(1H-1,2,4-triazol-1-yl)-6- (trifluoromethoxy)-3-((4-(trifluoromethoxy)phenyl)sulfonyl)quinoline 92

3-((4-butoxyphenyl)sulfonyl)-N-(4- methylpiperazin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 93

3-((4-butoxyphenyl)sulfonyl)-4-(1H- 1,2,4-triazol-1-yl)-6-(trifluoromethoxy)quinoline 94

3-((4-methoxyphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-nitroquinolin-4- amine 95

2-((3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)amino)ethan-1-ol 96

3-((3,4-dimethoxyphenyl)sulfonyl)-6,7- dimethoxy-4-(1H-1,2,4-triazol-1-yl)quinoline 97

3-((4-methoxyphenyl)sulfonyl)-6-nitro-4-(1H-1,2,4-triazol-1-yl)quinoline 98

2-(3-((4-methoxyphenyl)sulfonyl)-4-(1H- 1,2,4-triazol-1-yl)quinolin-6-yl)acetonitrile 99

2-(3-((4-methoxyphenyl)sulfonyl)-4-((4-methylpiperazin-1-yl)amino)quinolin-6- yl)acetonitrile 100

N,N-diethyl-2-(4-(3-((4- ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-1,4- diazepan-1-yl)ethan-1-amine 101

N,N-diethyl-2-((1-(3-((4- ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4- yl)piperidin-4-yl)oxy)ethan-1-amine 102

1′-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-[1,4′- bipiperidin]-4-ol 103

N,N-diethyl-1-(3-((4- ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4- yl)piperidin-4-amine 104

5-((3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)amino)pentan-1-ol 105

3-((4-ethylphenyl)sulfonyl)-N-(piperidin-1-yl)-6-(trifluoromethoxy)quinolin-4- amine 106

3-((4-ethylphenyl)sulfonyl)-N-(pyridin-4-ylmethyl)-6-(trifluoromethoxy)quinolin- 4-amine 107

3-((4-ethylphenyl)sulfonyl)-N-(pyridin-4-yl)-6-(trifluoromethoxy)quinolin-4-amine 108

3-((4-ethylphenyl)sulfonyl)-4-(1H-pyrrol-1-yl)-6-(trifluoromethoxy)quinoline 109

3-((4-ethylphenyl)sulfonyl)-4-(1H- pyrazol-1-yl)-6-(trifluoromethoxy)quinoline 110

3-((4-ethylphenyl)sulfonyl)-4-(1H-1,2,3- triazol-1-yl)-6-(trifluoromethoxy)quinoline 111

4-((3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)amino)butan-1-ol 112

4-(1H-benzo[d][1,2,3]triazol-1-yl)-3-((4- ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 113

1′-(3-((4-methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-[1,4′- bipiperidin]-4-ol 114

4-([1,4′-bipiperidin]-1′-yl)-3-((4- methoxyphenyl)sulfonyl)-6-nitroquinoline 115

2-(4-([1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)quinolin-6- yl)acetonitrile 116

4-([1,4′-bipiperidin]-1′-yl)-6-butoxy-3- ((3,4-dimethoxyphenyl)sulfonyl)quinoline 117

3-((4-ethylphenyl)sulfonyl)-4-(4-methyl- 1H-imidazol-1-yl)-6-(trifluoromethoxy)quinoline 118

3-((4-ethylphenyl)sulfonyl)-4-(1H- imidazol-1-yl)-6-(trifluoromethoxy)quinoline 119

4-([1,4′-bipiperidin]-1′-yl)-3-((4- butoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 120

4-([1,4′-bipiperidin]-1′-yl)-6- (trifluoromethoxy)-3-((4-(trifluoromethoxy)phenyl)sulfonyl)quinoline 121

4-([1,4′-bipiperidin]-1′-yl)-3-((3,4- dimethoxyphenyl)sulfonyl)-6-(methylthio)quinoline 122

4-([1,4′-bipiperidin]-1′-yl)-3-((3,4- dimethoxyphenyl)sulfonyl)-6,7-dimethoxyquinoline 123

6-butoxy-3-((3,4- dimethoxyphenyl)sulfonyl)-N,N- diethylquinolin-4-amine124

N,N-dibutyl-3-((3,4- dimethoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-amine 125

3-((4-ethylphenyl)sulfonyl)-4-(1H- tetrazol-1-yl)-6-(trifluoromethoxy)quinoline 126

N-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)morpholin-4-amine 127

4-(4-ethylphenyl)-1-(3-((4- ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4- yl)piperidin-4-ol 128

ethyl 4-(4-(4-ethylphenyl)-4- hydroxypiperidin-1-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6- carboxylate 129

4-(4-ethylphenyl)-1-(3-((4- methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4- yl)piperidin-4-ol 130

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4- hydroxy-[1,4′-bipiperidin]-1′-yl)quinoline-6-carboxylate 131

ethyl 4-(4-(2-(diethylamino)ethyl)-1,4- diazepan-1-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6- carboxylate 132

ethyl 4-(4-(2- (diethylamino)ethoxy)piperidin-1-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6- carboxylate 133

ethyl 4-(1H-benzo[d][1,2,3]triazol-1-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6- carboxylate 134

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(1H-imidazol-1-yl)quinoline-6-carboxylate 135

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(3-hydroxypiperidin-1-yl)quinoline-6- carboxylate 136

ethyl 4-([1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 137

ethyl 4-(3-hydroxypiperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 138

ethyl 4-(4-hydroxy-[1,4′-bipiperidin]-1′- yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 139

ethyl 4-(4-(2-(diethylamino)ethyl)-1,4- diazepan-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 140

ethyl 4-(4-(2- (diethylamino)ethoxy)piperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 141

ethyl 4-(1H-imidazol-1-yl)-3-((4- methoxyphenyl)sulfonyl)quinoline-6-carboxylate 142

ethyl 4-(1H-benzo[d][1,2,3]triazol-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline- 6-carboxylate 143

4-([1,4′-bipiperidin]-1′-yl)-3-((4- methoxyphenyl)sulfonyl)-N-methylquinoline-6-carboxamide 144

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6- carboxylate 145

1-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)-4-(4-methoxyphenyl)piperidin-4-ol 146

1-(3-((4-ethylphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)-4-(3-methoxyphenyl)piperidin-4-ol 147

4-(benzo[d][1,3]dioxol-5-yl)-1-(3-((4- ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4- yl)piperidin-4-ol 148

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4-hydroxy-4-(4-methoxyphenyl)piperidin- 1-yl)quinoline-6-carboxylate 149

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4-hydroxy-4-(3-methoxyphenyl)piperidin- 1-yl)quinoline-6-carboxylate 150

4-(3-methoxyphenyl)-1-(3-((4- methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4- yl)piperidin-4-ol 151

3-((4-butoxyphenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-6-(trifluoromethoxy)quinoline 152

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-[1,4′- bipiperidin]-4-ol 153

1′-(3-((3,4-dimethoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-[1,4′- bipiperidin]-4-ol 154

3-((3,4-dimethoxyphenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-6-(methylthio)quinoline 155

ethyl 4-(dibutylamino)-3-((4- methoxyphenyl)sulfonyl)quinoline-6-carboxylate 156

ethyl 4-(bis(2-hydroxyethyl)amino)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 157

ethyl 4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)quinoline-6- carboxylate 158

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6- carboxylate 159

4-([1,4′-bipiperidin]-1′-yl)-3-((4- butoxyphenyl)sulfonyl)-6-(methylthio)quinoline 160

3-((4-butoxyphenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-6-(methylthio)quinoline 161

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4- hydroxy-[1,4′-bipiperidin]-1′-yl)quinoline-6-carboxylate 162

1′-(3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)quinolin-4-yl)-[1,4′-bipiperidin]-4-ol 163

3-((4-butoxyphenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-6-(methylsulfinyl)quinoline 164

3-((4-butoxyphenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-6-(methylsulfonyl)quinoline 165

N,N-diethyl-3-((4- methoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6- carboxamide 166

N-(2-(diethylamino)ethyl)-3-((4- methoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6- carboxamide 167

4-([1,4′-bipiperidin]-1′-yl)-3-((4- butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinoline 168

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-4-ol 169

4-([1,4′-bipiperidin]-1′-yl)-3-((4- butoxyphenyl)sulfonyl)-6-(methylsulfonyl)quinoline 170

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfonyl)quinolin-4-yl)-[1,4′- bipiperidin]-4-ol 171

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1- yl)quinoline-6-carboxylate 172

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1- yl)quinoline-6-carboxylate 173

ethyl 4-(4-(azepan-1-yl)piperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 174

ethyl 4-(3-hydroxy-[1,4′-bipiperidin]-1′- yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 175

ethyl 4-(4-(hydroxymethyl)-[1,4′- bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxylate 176

ethyl 4-(4-(azepan-1-yl)piperidin-1-yl)-3-((4-butoxyphenyl)sulfonyl)quinoline-6- carboxylate 177

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(3- hydroxy-[1,4′-bipiperidin]-1′-yl)quinoline-6-carboxylate 178

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(hydroxymethyl)-[1,4′-bipiperidin]-1′- yl)quinoline-6-carboxylate 179

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan- 1-yl)quinoline-6-carboxylate180

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(4-(2-(pyrrolidin-1-yl)ethyl)-1,4- diazepan-1-yl)quinoline-6-carboxylate181

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1- yl)quinoline-6-carboxylate 182

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-1- yl)quinoline-6-carboxylate183

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinoline-6- carboxylate 184

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(1H-1,2,3-triazol-1-yl)quinoline-6- carboxylate 185

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(1H-tetrazol-1-yl)quinoline-6-carboxylate 186

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-tetrazol-1-yl)quinoline-6-carboxylate 187

4-(3-((4-butoxyphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)thiomorpholine 188

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinoline-6- carboxylate 189

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-1,2,3-triazol-1-yl)quinoline-6- carboxylate 190

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinoline-6- carboxylate 191

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-thiomorpholinoquinoline-6-carboxylate 192

3-((4-butoxyphenyl)sulfonyl)-N- isopropyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 193

3-((4-butoxyphenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-N-((4R,5S,6R)-2,4,5-trihydroxy-6- (hydroxymethyl)tetrahydro-2H-pyran-3-yl)quinoline-6-carboxamide 194

ethyl 3-((4-butoxyphenyl)sulfonyl)-4- (1H-imidazol-1-yl)quinoline-6-carboxylate 195

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1-oxidothiomorpholino)quinoline-6- carboxylate 196

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1,1-dioxidothiomorpholino)quinoline-6- carboxylate 197

4-(3-((4-butoxyphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)thiomorpholine 1-oxide 198

4-(3-((4-butoxyphenyl)sulfonyl)-6- (trifluoromethoxy)quinolin-4-yl)thiomorpholine 1,1-dioxide 199

3-((4-butoxyphenyl)sulfonyl)-N,N- diethyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 200

3-((4-butoxyphenyl)sulfonyl)-N-(2-hydroxyethyl)-4-(4-methyl-1,4-diazepan- 1-yl)quinoline-6-carboxamide 201

4-([1,4′-bipiperidin]-1′-yl)-3-((4- butoxyphenyl)sulfonyl)-N,N-diethylquinoline-6-carboxamide 202

4-([1,4′-bipiperidin]-1′-yl)-3-((4- butoxyphenyl)sulfonyl)-N-(2-hydroxyethyl)quinoline-6-carboxamide 203

4-([1,4′-bipiperidin]-1′-yl)-3-((4- butoxyphenyl)sulfonyl)-N-ethylquinoline-6-carboxamide 204

4-(1H-imidazol-1-yl)-3-((4- methoxyphenyl)sulfonyl)-N-((4R,5S,6R)-2,4,5-trihydroxy-6- (hydroxymethyl)tetrahydro-2H-pyran-3-yl)quinoline-6-carboxamide 205

4-(1H-benzo[d][1,2,3]triazol-1-yl)-3-((4-methoxyphenyl)sulfonyl)-N-((4R,5S,6R)- 2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3- yl)quinoline-6-carboxamide 206

3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 207

3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)-4-(4-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 208

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-3-ol 209

3-((4-butoxyphenyl)sulfonyl)-6- (methylsulfinyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 210

3-((4-butoxyphenyl)sulfonyl)-6- (methylsulfinyl)-4-(4-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 211

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1- yl)quinoline-6-carboxylate 212

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-morpholinopiperidin-1-yl)quinoline-6- carboxylate 213

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-fluorophenyl)piperazin-1-yl)quinoline- 6-carboxylate 214

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4- (4-(2-hydroxyethyl)piperazin-1-yl)piperidin-1-yl)quinoline-6-carboxylate 215

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-phenyl-[1,4′-bipiperidin]-1′-yl)quinoline- 6-carboxylate 216

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-butoxyphenyl)sulfonyl)quinoline-6- carboxylate 217

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-thiomorpholinopiperidin-1-yl)quinoline- 6-carboxylate 218

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-6-(methylthio)quinoline 219

4-([1,4′-bipiperidin]-1′-yl)-3-((4- (heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 220

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4- methyl-1,4-diazepan-1-yl)-6-(methylsulfinyl)quinoline 221

4-([1,4′-bipiperidin]-1′-yl)-3-((4- (heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 222

1′-(3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)quinolin-4-yl)-[1,4′-bipiperidin]-3-ol 223

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-[1,4′- bipiperidin]-4-ol 224

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-4-ol 225

ethyl 3-((4-methoxyphenyl)sulfonyl)-4- ((4-methylpiperazin-1-yl)amino)quinoline-6-carboxylate 226

3-((4-methoxyphenyl)sulfonyl)-N-(4- methylpiperazin-1-yl)-6-(methylthio)quinolin-4-amine 227

3-((4-methoxyphenyl)sulfonyl)-N-(4- methylpiperazin-1-yl)-6-(methylsulfinyl)quinolin-4-amine 228

3-((4-methoxyphenyl)sulfonyl)-N-(4- methylpiperazin-1-yl)-6-(methylsulfonyl)quinolin-4-amine 229

4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4- yl)morpholine 230

2-(4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethan-1-ol 231

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4- butoxyphenyl)sulfonyl)-6-(methylthio)quinoline 232

1′-(3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)quinolin-4-yl)-4-phenyl-[1,4′-bipiperidin]-4-ol 233

3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-(4-fluorophenyl)piperazin-1-yl)piperidin-1- yl)-6-(methylthio)quinoline 234

3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)- 6-(methylthio)quinoline 235

4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)morpholine 236

2-(4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethan-1-ol237

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4- butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinoline 238

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-4-phenyl- [1,4′-bipiperidin]-4-ol 239

3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-(4-fluorophenyl)piperazin-1-yl)piperidin-1- yl)-6-(methylsulfinyl)quinoline240

(1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-4-yl)methanol 241

3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)- 6-(methylsulfinyl)quinoline242

N,N-diethyl-2-(4-((4-(4-methyl-1,4-diazepan-1-yl)-6-(methylthio)quinolin-3-yl)sulfonyl)phenoxy)ethan-1-amine 243

4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4- yl)thiomorpholine 244

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(1-oxidothiomorpholino)piperidin-1- yl)quinoline-6-carboxylate 245

4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)thiomorpholine 246

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)- 6-(methylthio)quinoline 247

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-[1,4′- bipiperidin]-3-ol 248

3-((4-(heptyloxy)phenyl)sulfonyl)-6- (methylthio)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 249

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1- yl)-6-(methylthio)quinoline 250

2-(4-(1-(3-((4- (heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethan-1-ol 251

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6- (methylthio)quinoline 252

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4- methylpiperazin-1-yl)-6-(methylthio)quinoline 253

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)- 6-(methylsulfinyl)quinoline 254

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-3-ol 255

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 256

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1- yl)-6-(methylsulfinyl)quinoline257

2-(4-(1-(3-((4- (heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethan-1-ol258

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 259

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4- methylpiperazin-1-yl)-6-(methylsulfinyl)quinoline 260

3-((4-methoxyphenyl)sulfonyl)-4-((4- methylpiperazin-1-yl)amino)-N-((4R,5S,6R)-2,4,5-trihydroxy-6- (hydroxymethyl)tetrahydro-2H-pyran-3-yl)quinoline-6-carboxamide 262

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-4-phenyl- [1,4′-bipiperidin]-4-ol 263

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-4-phenyl- [1,4′-bipiperidin]-4-ol 264

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-6- (methylsulfinyl)quinoline 265

1′-(3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-3-ol 266

3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 267

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)- 6-(methylsulfinyl)quinoline268

2-(4-(1-(3-((4- (decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethan-1-ol269

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4- (decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 270

1′-(3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-4-phenyl- [1,4′-bipiperidin]-4-ol 271

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4- (4-(2-mPEGoxyethyl)piperazin-1-yl)piperidin-1-yl)-6- (methylthio)quinoline 272

3-((4-(heptyloxy)phenyl)sulfonyl)-6- (methylthio)-4-(4-(2-(pyrrolidin-1-yl)ethyl)piperazin-1-yl)quinoline 273

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)- 6-(methylthio)quinoline 274

4-(4-(1-benzylpyrrolidin-3-yl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)- 6-(methylthio)quinoline 275

4-(4-((1-benzylpiperidin-4- yl)methyl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6- (methylthio)quinoline 276

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(pyrrolidin-1-yl)ethyl)piperazin-1-yl)quinoline 277

4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 278

4-(4-(1-benzylpyrrolidin-3-yl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)- 6-(methylsulfinyl)quinoline 279

4-(4-((1-benzylpiperidin-4- yl)methyl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 280

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4- (4-(2-mPEGoxyethyl)piperazin-1-yl)piperidin-1-yl)-6- (methylsulfinyl)quinoline 281

3-((4-(heptyloxy)phenyl)sulfonyl)-6- (methylthio)-4-(4-(2-(piperidin-1-yl)ethyl)piperazin-1-yl)quinoline 282

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(piperidin-1- yl)ethyl)piperazin-1-yl)quinoline283

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)-6- (methylsulfinyl)quinoline 284

2-(4-(1-(3-((4-((3,7- dimethyloctyl)oxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethan-1-ol285

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 286

4-(1′-(3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-4-yl)morpholine 287

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 288

1″-(3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 289

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4- ((3,7-dimethyloctyl)oxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 290

([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(decyloxy)-3-fluorophenyl)sulfonyl)-6- (methylsulfinyl)quinoline 291

2-(4-(1-(3-((4-(decyloxy)-3- fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethan-1-ol292

2-(4-(1′-(3-((4- (decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethan-1- ol 293

N,N-diethyl-6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-amine 294

N-ethyl-N-isopropyl-6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4- amine 295

N,N-dibutyl-6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-amine 296

N1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-N1,N2,N2-triethylethane-1,2-diamine 297

N1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-N2,N2-diethylethane-1,2-diamine 298

N1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-N3,N3-diethylpropane-1,3-diamine 299

N1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-N4,N4-diethylbutane-1,4-diamine 300

N3-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-N1,N1-diethylbutane-1,3-diamine 301

2-(4-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperazin-1-yl)ethan-1-ol 302

3-(4-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperazin-1-yl)-N,N-diethylpropan-1- amine 303

1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-ol 304

(1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-3-yl)methanol 305

1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)pyrrolidin-3-ol 306

6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)-4-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2- yl)quinoline 307

4-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-N,N-dimethyl-1,4-diazepane-1- carboxamide 308

1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-4-phenylpiperidin-4-ol 309

methyl 4-(1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)benzoate 310

4-(1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)-N-methylbenzamide 311

6,7-dimethoxy-4-(4-(4- methoxyphenyl)piperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline 312

6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)-4-(4-(4-(pyrrolidin-1-ylmethyl)phenyl)piperidin- 1-yl)quinoline 313

6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)-4-(3-phenylpyrrolidin-1-yl)quinoline 314

4-(3-(benzo[d][1,3]dioxol-5- yl)pyrrolidin-1-yl)-6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinoline 315

6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)-4-(4-phenylpiperazin-1-yl)quinoline 316

6,7-dimethoxy-4-(4-(4- methoxyphenyl)piperazin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline 317

ethyl 4-(4-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperazin-1-yl)benzoate 318

4-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-1-(4-methoxyphenyl)piperazin-2-one 319

N-cyclohexyl-4-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4- yl)piperazin-1-yl)benzamide 320

4-([1,4′-bipiperidin]-1′-yl)-6,7- dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinoline 321

1-(1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)pyrrolidin-2-one 322

(1-(1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)pyrrolidin-2- yl)methanol 323

2-(4-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-1,4-diazepan-1-yl)ethan-1-ol 324

7-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-1-isobutyldecahydropyrido[4,3- e][1,4]oxazepine 325

1-((4-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-1,4-diazepan-1-yl)methyl)cyclopentan-1- ol 326

6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)-4-(4-(oxetan-3-yl)-1,4-diazepan-1-yl)quinoline 327

6-chloro-2-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-1,4-diazepan-1-yl)benzo[d]thiazole 328

1-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-4-methyl-1,4-diazepan-5-one 329

6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)-4-(4-(tetrahydro-2H-thiopyran-4-yl)-1,4- diazepan-1-yl)quinoline 330

4-(4-(6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-4-yl)-1,4-diazepan-1-yl)tetrahydro-2H- thiopyran 1,1-dioxide 331

4-([1,4′-bipiperidin]-1′-yl)-3-((4- methoxyphenyl)sulfonyl)-N,N-dimethylquinoline-6-carboxamide 332

3-((4-methoxyphenyl)sulfonyl)-N,N- dimethyl-4-(4-(2-oxopyrrolidin-1-yl)piperidin-1-yl)quinoline-6-carboxamid 333

4-(4-(2-(dimethylamino)-2-oxoethyl)-1,4- diazepan-1-yl)-3-((4-methoxyphenyl)sulfonyl)-N,N- dimethylquinoline-6-carboxamide 334

4-([1,4′-bipiperidin]-1′-yl)-3-((4- methoxyphenyl)sulfonyl)-N-methylquinoline-6-carboxamide 335

3-((4-methoxyphenyl)sulfonyl)-N- methyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 336

4-(4-(2-(hydroxymethyl)pyrrolidin-1- yl)piperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)-N- methylquinoline-6-carboxamide 337

4-([1,4′-bipiperidin]-1′-yl)-N-(2- (diethylamino)ethyl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6- carboxamide 338

N-(2-(diethylamino)ethyl)-4-(1- isobutyloctahydropyrido[4,3-e][1,4]oxazepin-7(5H)-yl)-3-((4- methoxyphenyl)sulfonyl)quinoline-6-carboxamide 339

2-(4-(1-(3-((4- (dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethan-1-ol340

2-(4-(1′-(3-((4- (dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethan-1- ol 341

3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4- (4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6- (methylsulfinyl)quinoline 342

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 343

1″-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)- [1,4′:1′,4″-terpiperidin]-3-ol 344

2-(4-(1-(6-(methylsulfinyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan- 1-ol 345

2-(4-(1′-(6-(methylsulfinyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1- yl)ethan-1-ol 346

4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(tetradecyloxy)phenyl)sulfonyl)quinoline 347

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-6-(methyl(λ¹-oxidanyl)-λ³-sulfanyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinoline 348

1″-(6-(methyl(λ¹-oxidanyl)-λ³-sulfanyl)- 3-((4-(tetradecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 349

1-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4- yl)pyrrolidin-2-one 350

(1-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4- yl)pyrrolidin-2-yl)methanol 351

2-(4-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-1,4-diazepan- 1-yl)ethan-1-ol 352

7-(3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)quinolin-4-yl)-1-isobutyldecahydropyrido[4,3- e][1,4]oxazepine 353

4-(3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)quinolin-4-yl)-N-(2,2,2-trifluoroethyl)-1,4-diazepane-1- sulfonamide 354

1-((4-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-1,4-diazepan- 1-yl)methyl)cyclopentan-1-ol355

3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)-4-(4-(oxetan-3-yl)-1,4-diazepan-1-yl)quinoline 356

2-(4-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-1,4-diazepan- 1-yl)-6-chlorobenzo[d]thiazole357

1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-4-methyl-1,4- diazepan-5-one 358

3-((4-butoxyphenyl)sulfonyl)-6- (methylthio)-4-(4-(tetrahydro-2H-thiopyran-4-yl)-1,4-diazepan-1- yl)quinoline 359

4-(4-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-1,4-diazepan- 1-yl)tetrahydro-2H-thiopyran1,1-dioxide 360

3-((4-methoxyphenyl)sulfonyl)-N- methyl-4-(methylamino)quinoline-6-carboxamide 361

1-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4- yl)pyrrolidin-2-one 362

2-(4-(1-(3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethanol 363

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-6- (methylsulfinyl)quinoline 364

1″-(3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 365

2-(4-(1-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethanol 366

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)- 6-(methylsulfinyl)quinoline367

1″-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 368

2-(4-(1′-(3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 369

2-(4-(1′-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 370

3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 371

3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 372

1″-(3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-4-ol 373

1″-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-4-ol 374

1″-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)- [1,4′:1′,4″-terpiperidin]-4-ol 375

1″-(6-(methylsulfinyl)-3-((4- (tetradecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-4-ol 376

2-(4-(1-(3-((4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4- yl)piperazin-1-yl)ethanol 377

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 378

1″-(3-((4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 379

3-((4-methoxyphenyl)sulfonyl)-N,N- dimethyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 380

2-(4-(1-(6-(methylsulfinyl)-3-((4-(undecyloxy)phenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethanol 381

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-6- (methylsulfinyl)-3-((4-(undecyloxy)phenyl)sulfonyl)quinoline 382

1″-(6-(methylsulfinyl)-3-((4- (undecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-4-ol 383

1″-(6-(methylsulfinyl)-3-((4- (undecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 384

2-(4-((4-([1,4′:1′,4″-terpiperidin]-1″-yl)-6-(methylsulfinyl)quinolin-3- yl)sulfonyl)phenoxy)-N,N- diethylethanamine385

2-(4-(1′-(3-((4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 386

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 387

2-(4-(1′-(3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 388

3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 389

1″-(3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 390

4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 391

3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 392

3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 393

4-(1′-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-4-yl)morpholine 394

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 395

3-((2-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 396

3-((3,5-difluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 397

3-((2,3-difluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 398

4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(octadecyloxy)phenyl)sulfonyl)quinoline 399

3-((3-fluoro-4- (octadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 400

4-(1′-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′- bipiperidin]-4-yl)thiomorpholine401

1-(4-(1′-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanone 402

3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfonyl)quinoline 403

(S)-1″-(3-((4- (dodecyloxy)phenyl)sulfonyl)-6-((S)-methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 404

(S)-1″-(3-((4- (dodecyloxy)phenyl)sulfonyl)-6-((R)-methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 405

(R)-1″-(3-((4- (dodecyloxy)phenyl)sulfonyl)-6-((S)-methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 406

(R)-1″-(3-((4- (dodecyloxy)phenyl)sulfonyl)-6-((R)-methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″- terpiperidin]-3-ol 407

(R)-2-(4-(1′-(3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 408

(S)-2-(4-(1′-(3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 409

(R)-2-(4-(1′-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 410

(S)-2-(4-(1′-(3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 411

3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 412

3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 413

3-((4-(dodecyloxy)-3- fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 414

4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 415

3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 416

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 417

3-((4-(dodecyloxy)-2,3- difluorophenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 418

3-((4-(dodecyloxy)-2,3- difluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 419

3-((4-(dodecyloxy)-2,3- difluorophenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 420

3-((4-(dodecyloxy)-2,3- difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 421

3-((2,3-difluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 422

3-((2,3-difluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 423

3-((2,3-difluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 424

3-((2,3-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 425

3-((2,3-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 426

3-((2,3-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 427

3-((2,3-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 428

3-((4-(dodecyloxy)-3,5- difluorophenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 429

3-((4-(dodecyloxy)-3,5- difluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 430

3-((4-(dodecyloxy)-3,5- difluorophenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 431

3-((4-(dodecyloxy)-3,5- difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 432

3-((3,5-difluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 433

3-((3,5-difluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 434

3-((3,5-difluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 435

3-((3,5-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 436

3-((3,5-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 437

3-((3,5-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 438

3-((3,5-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 439

3-((4-(dodecyloxy)-2- fluorophenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 440

3-((4-(dodecyloxy)-2- fluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 441

3-((4-(dodecyloxy)-2- fluorophenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 442

3-((4-(dodecyloxy)-2- fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 443

4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((2-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 444

3-((2-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 445

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 446

3-((2-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 447

4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((2-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 448

3-((2-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 449

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 450

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4- (dodecyloxy)-2,3-difluorophenyl)sulfonyl)-6- (methylsulfinyl)quinoline 451

3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 452

3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 453

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(tetradecyloxy)phenyl)sulfonyl)quinoline 454

4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(tetradecyloxy)phenyl)sulfonyl)quinoline 455

(R)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(octadecyloxy)phenyl)sulfonyl)quinoline 456

(S)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(octadecyloxy)phenyl)sulfonyl)quinoline 457

(R)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(octadecyloxy)phenyl)sulfonyl)quinoline 458

(S)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(octadecyloxy)phenyl)sulfonyl)quinoline 459

(R)-4-(4-(4-cyclopropylpiperazin-1-yl)- [1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4- (octadecyloxy)phenyl)sulfonyl)quinoline 460

(S)-4-(4-(4-cyclopropylpiperazin-1-yl)- [1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4- (octadecyloxy)phenyl)sulfonyl)quinoline 461

3-((4-(icosyloxy)phenyl)sulfonyl)-4-(4- (4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6- (methylsulfinyl)quinoline 462

4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 463

(R)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 464

(S)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 465

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4- (4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6- (methylsulfinyl)quinoline 466

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 467

(R)-3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 468

(S)-3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 469

(R)-3-((4-(dodecyloxy)-2,3- difluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 470

(S)-3-((4-(dodecyloxy)-2,3- difluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 471

(R)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 472

(S)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((3-fluoro-4- (tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 473

(R)-3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 474

(S)-3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 475

(R)-3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 476

(S)-3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 477

(R)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(octadecyloxy)phenyl)sulfonyl)quinoline 478

(S)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(octadecyloxy)phenyl)sulfonyl)quinoline 479

(R)-4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 480

(S)-4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 481

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylthio)quinoline 482

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfonyl)quinoline 483

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 484

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 485

(R)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4- (icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 486

(S)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4- (icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 487

(R)-3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 488

(S)-3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 489

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3- ((4-(tetracosyloxy)phenyl)sulfonyl)quinoline 490

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)-3- ((4-(tetracosyloxy)phenyl)sulfonyl)quinoline 491

4-(4-(4-ethylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((4-(hexacosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 492

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(hexacosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 493

3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(4-propylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)quinoline 494

4-(4-(4-butylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 495

3-((4-(docosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(4-propylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)quinoline 496

4-(4-(4-butylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-3-((4-(docosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 497

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylthio)quinoline 498

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′- bipiperidin]-1′-yl)-6-(methylsulfonyl)quinoline 499

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6- (methylthio)quinoline 500

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 501

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6- methoxyquinoline 502

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6- (trifluoromethoxy)quinoline 503

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 504

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 505

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-methoxyquinoline 506

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 507

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylthio)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 508

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)-3- ((4-(octadecyloxy)phenyl)sulfonyl)quinoline 509

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-methoxy-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 510

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(octadecyloxy)phenyl)sulfonyl)-6- (trifluoromethoxy)quinoline 511

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (octadecyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 512

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (octadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 513

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (octadecyloxy)phenyl)sulfonyl)-6-methoxyquinoline 514

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (octadecyloxy)phenyl)sulfonyl)-6-methoxyquinoline 515

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- (methylthio)quinoline 516

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 517

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- methoxyquinoline 518

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin- 1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6- (trifluoromethoxy)quinoline 519

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (icosyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 520

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 521

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (icosyloxy)phenyl)sulfonyl)-6-methoxyquinoline 522

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4- (icosyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 523

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylthio)quinoline 524

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 525

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-methoxyquinoline 526

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 527

3-((4-(docosyloxy)-3- fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylthio)quinoline 528

3-((4-(docosyloxy)-3- fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 529

3-((4-(docosyloxy)-3- fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-methoxyquinoline530

3-((4-(docosyloxy)-3- fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 531

3-((4-(docosyloxy)-3,5- difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 532

3-((4-(docosyloxy)-2,3- difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 533

3-((4-(docosyloxy)-2- fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 534

3-((3,5-difluoro-4- (icosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 535

3-((2,3-difluoro-4- (icosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 536

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4- (icosyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 537

3-((3,5-difluoro-4- (octadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 538

3-((2,3-difluoro-4- (octadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 539

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4- (octadecyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 540

3-((3,5-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 541

3-((2,3-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 542

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4- (hexadecyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 543

3-((2,6-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 544

3-((2,6-difluoro-4- (octadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 545

3-((2,6-difluoro-4- (icosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 546

3-((4-(docosyloxy)-2,6- difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 547

3-((2,5-difluoro-4- (hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 548

3-((2,5-difluoro-4- (octadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 549

3-((2,5-difluoro-4- (icosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 550

3-((4-(docosyloxy)-2,5- difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1- yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline

In certain embodiments, provided is a salt of a compound of thisdisclosure. In certain embodiments, the salt is salt of a compound ofthis disclosure formed with hydrochloric acid, hydrochloric acid,phosphoric acid, methanesulfonic acid (mesylate salt), malic acid,malonic acid, maleic acid, fumaric acid, tartaric acid, citric acid,acetic acid, or oxalic acid. In certain embodiments, the salt is a saltof a compound of this disclosure formed with methanesulfonic acid(mesylate salt). In certain embodiments, the salt is a salt of acompound of this disclosure formed with oxalic acid. In any of theseembodiments, the salt is a salt of a compound of this disclosure formedwith oxalic acid dihydrate. In any of these embodiments, the salt is atris(oxalic acid dihydrate) salt.

3. Methods

The methods described herein may be applied to cell populations in vivoor ex vivo. “In vivo” means within a living individual, as within ananimal or human. In this context, the methods described herein may beused therapeutically in an individual. “Ex vivo” means outside of aliving individual. Examples of ex vivo cell populations include in vitrocell cultures and biological samples including fluid or tissue samplesobtained from individuals. Such samples may be obtained by methods wellknown in the art. Exemplary biological fluid samples include blood,cerebrospinal fluid, urine and saliva. In this context, the compoundsand compositions described herein may be used for a variety of purposes,including therapeutic and experimental purposes. For example, thecompounds and compositions described herein may be used ex vivo todetermine the optimal schedule and/or dosing of administration of acompound of the present disclosure for a given indication, cell type,individual, and other parameters. Information gleaned from such use maybe used for experimental purposes or in the clinic to set protocols forin vivo treatment. Other ex vivo uses for which the compounds andcompositions described herein may be suited are described below or willbecome apparent to those skilled in the art.

The present disclosure provides compounds and compositions for treatingpathogenic blood vessel disorders such as diabetic retinopathy,age-related macular degeneration (AMD), retinopathy of prematurity, orcancer. The treatment can be through killing tumor blood vessels. Insome embodiments, a tumor patient that can be suitably treated by thepresent technology expresses a plexin domain-containing protein (e.g.,PLXDC1 or PLXDC2). The expression may be on a tumor blood epithelialcell.

As noted, the present technology not only can inhibit growth of newtumor blood vessels, but can also kill existing tumor blood vessels,thereby treating the tumor. In some embodiments, therefore, a tumorpatient that can benefit from the present treatment is one that has atumor that has undergone tumor angiogenesis. In some embodiments, thetumor comprises a vascularized tumor. In some embodiments, the tumorbeing treat has a diameter that is greater than about 0.1, 0.2, 0.3,0.4, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9 or 10 cm (or any derivablerange therein). In some embodiments, the tumor already contains tumorblood vessels.

In some embodiments, the tumor does not have a known tumor surfacemarker as target for immunotherapy. In some embodiments, the tumor doesnot contain a mutant gene that serves as a target for tumor therapy. Insome embodiments, the therapy of the present disclosure does not includeinducing antibody-dependent cell-mediated cytotoxicity (ADCC). In someembodiments, a therapeutic agent of the present disclosure does notinduce ADCC.

In some embodiments, the patient suffers from a cancer such as,polycythemia vera, lymphomas (e.g., Hodgkin's disease and non-Hodgkin'sdisease), multiple myeloma, Waldenstrom's macroglobulinemia, heavy chaindisease, and solid tumors including, but not limited to, sarcomas andcarcinomas such as fibrosarcoma, myxosarcoma, liposarcoma,chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma,endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma,synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, thyroidcancer, endometrial cancer, melanoma, prostate cancer, ovarian cancer,prostate cancer, squamous cell carcinoma, basal cell carcinoma,adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma,papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma,medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma,hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonalcarcinoma, Wilm's tumor, cervical cancer, testicular tumor, lungcarcinoma, small cell lung carcinoma, bladder carcinoma, epithelialcarcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma,ependymoma, pinealoma, hemangioblastoma, acoustic neuroma,oligodendroglioma, menangioma, melanoma, neuroblastoma andretinoblastoma.

In some embodiments, the compounds and compositions described herein maybe used to treat any cancerous or pre-cancerous tumor, such as a solidtumor. Cancers that may be treated by compounds and compositionsprovided herein include, but are not limited to, cancer cells from thebladder, blood, bone, bone marrow, brain, breast, colon, esophagus,gastrointestine, gum, head, kidney, liver, lung, nasopharynx, neck,ovary, prostate, skin, stomach, testis, tongue, or uterus. In addition,the cancer may specifically be of the following histological type,though it is not limited to these: neoplasm, malignant; carcinoma;carcinoma, undifferentiated; giant and spindle cell carcinoma; smallcell carcinoma; papillary carcinoma; squamous cell carcinoma;lymphoepithelial carcinoma; basal cell carcinoma; pilomatrix carcinoma;transitional cell carcinoma; papillary transitional cell carcinoma;adenocarcinoma; gastrinoma, malignant; cholangiocarcinoma;hepatocellular carcinoma; combined hepatocellular carcinoma andcholangiocarcinoma; trabecular adenocarcinoma; adenoid cystic carcinoma;adenocarcinoma in adenomatous polyp; adenocarcinoma, familial polyposiscoli; solid carcinoma; carcinoid tumor, malignant; branchiolo-alveolaradenocarcinoma; papillary adenocarcinoma; chromophobe carcinoma;acidophil carcinoma; oxyphilic adenocarcinoma; basophil carcinoma; clearcell adenocarcinoma; granular cell carcinoma; follicular adenocarcinoma;papillary and follicular adenocarcinoma; nonencapsulating sclerosingcarcinoma; adrenal cortical carcinoma; endometrioid carcinoma; skinappendage carcinoma; apocrine adenocarcinoma; sebaceous adenocarcinoma;ceruminous adenocarcinoma; mucoepidermoid carcinoma; cystadenocarcinoma;papillary cystadenocarcinoma; papillary serous cystadenocarcinoma;mucinous cystadenocarcinoma; mucinous adenocarcinoma; signet ring cellcarcinoma; infiltrating duct carcinoma; medullary carcinoma; lobularcarcinoma; inflammatory carcinoma; mammary paget's disease; acinar cellcarcinoma; adenosquamous carcinoma; adenocarcinoma w/squamousmetaplasia; malignant thymoma; malignant ovarian stromal tumor;malignant thecoma; malignant granulosa cell tumor; and malignantroblastoma; sertoli cell carcinoma; malignant leydig cell tumor;malignant lipid cell tumor; malignant paraganglioma; malignantextra-mammary paraganglioma; pheochromocytoma; glomangiosarcoma;malignant melanoma; amelanotic melanoma; superficial spreading melanoma;malignant melanoma in giant pigmented nevus; epithelioid cell melanoma;malignant blue nevus; sarcoma; fibrosarcoma; malignant fibroushistiocytoma; myxosarcoma; liposarcoma; leiomyosarcoma;rhabdomyosarcoma; embryonal rhabdomyosarcoma; alveolar rhabdomyosarcoma;stromal sarcoma; malignant mixed tumor; mullerian mixed tumor;nephroblastoma; hepatoblastoma; carcinosarcoma; malignant mesenchymoma;malignant brenner tumor; malignant phyllodes tumor; synovial sarcoma;malignant mesothelioma; dysgerminoma; embryonal carcinoma; malignantteratoma; malignant struma ovarii; choriocarcinoma; malignantmesonephroma; hemangiosarcoma; malignant hemangioendothelioma; kaposi'ssarcoma; malignant hemangiopericytoma; lymphangiosarcoma; osteosarcoma;juxtacortical osteosarcoma; chondrosarcoma; malignant chondroblastoma;mesenchymal chondrosarcoma; giant cell tumor of bone; ewing's sarcoma;malignant odontogenic tumor; ameloblastic odontosarcoma; malignantameloblastoma; ameloblastic fibrosarcoma; malignant pinealoma; chordoma;malignant glioma; ependymoma; astrocytoma; protoplasmic astrocytoma;fibrillary astrocytoma; astroblastoma; glioblastoma; oligodendroglioma;oligodendroblastoma; primitive neuroectodermal; cerebellar sarcoma;ganglioneuroblastoma; neuroblastoma; retinoblastoma; olfactoryneurogenic tumor; malignant meningioma; neurofibrosarcoma; malignantneurilemmoma; malignant granular cell tumor; malignant lymphoma;Hodgkin's disease; Hodgkin's lymphoma; paragranuloma; small lymphocyticmalignant lymphoma; diffuse large cell malignant lymphoma; follicularmalignant lymphoma; mycosis fungoides; other specified non-Hodgkin'slymphomas; malignant histiocytosis; multiple myeloma; mast cell sarcomaor immunoproliferative small intestinal disease.

In some embodiments, the subject has cancer, optionally comprising asolid tumor. An agent disclosed herein may be administered locally tothe tumor. In some embodiments, the tumor is an adenocarcinoma, anadrenal tumor, an anal tumor, a bile duct tumor, a bladder tumor, a bonetumor, a blood born tumor, a brain/CNS tumor, a breast tumor, a cervicaltumor, a colorectal tumor, an endometrial tumor, an esophageal tumor, anEwing tumor, an eye tumor, a gallbladder tumor, a gastrointestinal, akidney tumor, a laryngeal or hypopharyngreal tumor, a liver tumor, alung tumor, a mesothelioma tumor, a multiple myeloma tumor, a muscletumor, a nasopharyngeal tumor, a neuroblastoma, an oral tumor, anosteosarcoma, an ovarian tumor, a pancreatic tumor, a penile tumor, apituitary tumor, a primary tumor, a prostate tumor, a retinoblastoma, aRhabdomyosarcoma, a salivary gland tumor, a soft tissue sarcoma, amelanoma, a metastatic tumor, a basal cell carcinoma, a Merkel celltumor, a testicular tumor, a thymus tumor, a thyroid tumor, a uterinetumor, a vaginal tumor, a vulvar tumor, or a Wilms tumor. In someembodiments, a compound and/or composition described herein may beadministered parenterally, at or near the site of a tumor, or distantfrom the site of the tumor.

Actual dosage levels of the active ingredients in the pharmaceuticalcompositions may be varied so as to obtain an amount of the activeingredient which is effective to achieve the desired therapeuticresponse for a particular patient, composition, and mode ofadministration, without being toxic to the patient.

The selected dosage level will depend upon a variety of factorsincluding the activity of the particular agent employed, the route ofadministration, the time of administration, the rate of excretion ormetabolism of the particular compound being employed, the duration ofthe treatment, other drugs, compounds and/or materials used incombination with the particular compound employed, the age, sex, weight,condition, general health and prior medical history of the patient beingtreated, and like factors well known in the medical arts.

A physician or veterinarian having ordinary skill in the art can readilydetermine and prescribe the effective amount of the pharmaceuticalcomposition required. For example, the physician or veterinarian couldprescribe and/or administer doses of the compounds employed in thepharmaceutical composition at levels lower than that required in orderto achieve the desired therapeutic effect and gradually increase thedosage until the desired effect is achieved.

The administration of one or more compounds as described herein mayresult in at least a 10% decrease (e.g., at least 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or even 100%decrease in one or more symptoms of a disease or condition, such as adecrease in tumor size.

Compounds described herein can be used in methods for agonizingPigment-Epithelium-Derived Factor (PEDF) receptors. Compounds describedherein can also be used in methods for inhibiting angiogenesis.

The PEDF receptors have been identified as two homologous membraneproteins called plexin domain containing 1 (PLXDC1) and plexin domaincontaining 2 (PLXDC2). They belong to a new type of cell-surfacereceptors and are the only proteins that are known to confercell-surface binding to PEDF and to transduce PEDF signal into thetarget cells. Consistent with the ability of PEDF to suppress pathogenicangiogenesis in blinding diseases and in cancer without affectinghealthy blood vessels, the PEDF receptors are highly expressed inpathogenic blood vessels in many diseases, including tumor blood vesselsand diabetic retinopathy. The PEDF receptors are not detected in healthyblood vessels. One of the PEDF receptors (TEM7, PLXDC1) was well studiedin the past as a tumor endothelial marker that is enriched in tumorblood vessels of diverse types of human cancer including colon, liver,lung, breast, pancreatic, brain, bladder, ovarian, kidney, esophagus,gastric and endometrial cancer and Kaposi sarcoma, liposarcoma andsynovial sarcoma. In blinding diseases, PEDF receptor TEM7 (PLXDC1) ishighly expressed in pathogenic blood vessels of diabetic retinopathy,retinal occlusive vascular disease, retinopathy of prematurity, andchoroidal neovascularization (pathogenic angiogenesis in AMD). This isconsistent with the role of PEDF in suppressing pathogenic angiogenesisin these diseases without affecting healthy blood vessels.

The compounds and methods described herein can therefore be used intreating disease mediated by PEDF receptors or associated withangiogenesis, such as cancer, retinal occlusive vascular disease,retinopathy of prematurity, diabetic retinopathy, and age-relatedmacular degeneration.

In certain embodiments, provided herein are methods for agonizingPigment-Epithelium-Derived Factor (PEDF) receptors in a patient in needthereof comprising administering to said patient a therapeuticallyeffective amount of a compound of the disclosure, or a pharmaceuticallyacceptable salt, isotopically enriched analog, stereoisomer, mixture ofstereoisomers, or tautomer thereof.

In certain embodiments, provided herein are methods for inhibitingangiogenesis in a patient in need thereof comprising administering tosaid patient a therapeutically effective amount of a compound of thedisclosure, or a pharmaceutically acceptable salt, isotopically enrichedanalog, stereoisomer, mixture of stereoisomers, or tautomer thereof. Incertain embodiments, the angiogenesis is pathogenic angiogenesis.

Also provided herein are methods for treating a disease or disordermediated by PEDF receptors in a patient in need thereof comprisingadministering to said patient a therapeutically effective amount of acompound of the disclosure, or a pharmaceutically acceptable salt,isotopically enriched analog, stereoisomer, mixture of stereoisomers, ortautomer thereof.

Also provided herein are methods for treating a disease or disorderassociated with angiogenesis in a patient in need thereof comprisingadministering to said patient a therapeutically effective amount of acompound of the disclosure, or a pharmaceutically acceptable salt,isotopically enriched analog, stereoisomer, mixture of stereoisomers, ortautomer thereof.

Also provided herein are methods for treating a disease or disorderselected from a cancer, retinal occlusive vascular disease, retinopathyof prematurity, diabetic retinopathy, and age-related maculardegeneration comprising administering to said patient a therapeuticallyeffective amount of a compound of the disclosure, or a pharmaceuticallyacceptable salt, isotopically enriched analog, stereoisomer, mixture ofstereoisomers, or tautomer thereof. In certain embodiments, the canceris selected from colon, liver, lung, breast, pancreatic, brain, bladder,ovarian, kidney, esophagus, gastric and endometrial cancer and Kaposisarcoma, liposarcoma and synovial sarcoma. In certain embodiments, thedisease is a blinding disease. In certain embodiments, the disease isdiabetic retinopathy, retinal occlusive vascular disease, retinopathy ofprematurity, or choroidal neovascularization (pathogenic angiogenesis inAMD).

In certain embodiments, provided herein is use of a compound of thedisclosure, or a pharmaceutically acceptable salt, isotopically enrichedanalog, stereoisomer, mixture of stereoisomers, or tautomer thereof in amethod for agonizing Pigment-Epithelium-Derived Factor (PEDF) receptorsin a patient in need thereof comprising administering to said patient atherapeutically effective amount of the compound, or a pharmaceuticallyacceptable salt, isotopically enriched analog, stereoisomer, mixture ofstereoisomers, or tautomer thereof.

In certain embodiments, provided herein is use of a compound of thedisclosure, or a pharmaceutically acceptable salt, isotopically enrichedanalog, stereoisomer, mixture of stereoisomers, or tautomer thereof in amethod for inhibiting angiogenesis in a patient in need thereofcomprising administering to said patient a therapeutically effectiveamount of the compound, or a pharmaceutically acceptable salt,isotopically enriched analog, stereoisomer, mixture of stereoisomers, ortautomer thereof. In certain embodiments, the angiogenesis is pathogenicangiogenesis.

Also provided herein is use of a compound of the disclosure, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof in a methodfor treating a disease or disorder mediated by PEDF receptors in apatient in need thereof comprising administering to said patient atherapeutically effective amount of the compound, or a pharmaceuticallyacceptable salt, isotopically enriched analog, stereoisomer, mixture ofstereoisomers, or tautomer thereof.

Also provided herein is use of a compound of the disclosure, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof in a methodfor treating a disease or disorder associated with angiogenesis in apatient in need thereof comprising administering to said patient atherapeutically effective amount of the compound, or a pharmaceuticallyacceptable salt, isotopically enriched analog, stereoisomer, mixture ofstereoisomers, or tautomer thereof.

Also provided herein is use of a compound of the disclosure, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof in a methodfor treating a disease or disorder selected from a cancer, retinalocclusive vascular disease, retinopathy of prematurity, diabeticretinopathy, and age-related macular degeneration comprisingadministering to said patient a therapeutically effective amount of thecompound, or a pharmaceutically acceptable salt, isotopically enrichedanalog, stereoisomer, mixture of stereoisomers, or tautomer thereof. Incertain embodiments, the cancer is selected from colon, liver, lung,breast, pancreatic, brain, bladder, ovarian, kidney, esophagus, gastricand endometrial cancer and Kaposi sarcoma, liposarcoma and synovialsarcoma. In certain embodiments, the disease is a blinding disease. Incertain embodiments, the disease is diabetic retinopathy, retinalocclusive vascular disease, retinopathy of prematurity, or choroidalneovascularization (pathogenic angiogenesis in AMD).

In certain embodiments, provided herein is use of a compound of thedisclosure, or a pharmaceutically acceptable salt, isotopically enrichedanalog, stereoisomer, mixture of stereoisomers, or tautomer thereof inthe manufacture of a medicament for agonizing Pigment-Epithelium-DerivedFactor (PEDF) receptors in a patient in need thereof.

In certain embodiments, provided herein is use of a compound of thedisclosure, or a pharmaceutically acceptable salt, isotopically enrichedanalog, stereoisomer, mixture of stereoisomers, or tautomer thereof inthe manufacture of a medicament for inhibiting angiogenesis in a patientin need thereof. In certain embodiments, the angiogenesis is pathogenicangiogenesis.

Also provided herein is use of a compound of the disclosure, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof in themanufacture of a medicament for treating a disease or disorder mediatedby PEDF receptors in a patient in need thereof.

Also provided herein is use of a compound of the disclosure, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof in themanufacture of a medicament for treating a disease or disorderassociated with angiogenesis in a patient in need thereof.

Also provided herein is use of a compound of the disclosure, or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof in themanufacture of a medicament for treating a disease or disorder selectedfrom a cancer, retinal occlusive vascular disease, retinopathy ofprematurity, diabetic retinopathy, and age-related macular degeneration.In certain embodiments, the cancer is selected from colon, liver, lung,breast, pancreatic, brain, bladder, ovarian, kidney, esophagus, gastricand endometrial cancer and Kaposi sarcoma, liposarcoma and synovialsarcoma. In certain embodiments, the disease is a blinding disease. Incertain embodiments, the disease is diabetic retinopathy, retinalocclusive vascular disease, retinopathy of prematurity, or choroidalneovascularization (pathogenic angiogenesis in AMD).

4. Kits

Provided herein are also kits that include a compound of the disclosure,or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, andsuitable packaging. In certain embodiments, a kit further includesinstructions for use. In one aspect, a kit includes a compound of thedisclosure, or a pharmaceutically acceptable salt, isotopically enrichedanalog, stereoisomer, mixture of stereoisomers, or tautomer thereof, anda label and/or instructions for use of the compounds in the treatment ofthe indications, including the diseases or conditions, described herein.

Provided herein are also articles of manufacture that include a compounddescribed herein or a pharmaceutically acceptable salt, isotopicallyenriched analog, stereoisomer, mixture of stereoisomers, or tautomerthereof in a suitable container. The container may be a vial, jar,ampoule, preloaded syringe and intravenous bag.

5. Pharmaceutical Compositions and Modes of Administration

Compounds provided herein are usually administered in the form ofpharmaceutical compositions. Thus, provided herein are alsopharmaceutical compositions that contain one or more of the compoundsdescribed herein or a pharmaceutically acceptable salt, isotopicallyenriched analog, stereoisomer, mixture of stereoisomers, or tautomerthereof (collectively and individually, the “active ingredient”) and oneor more pharmaceutically acceptable vehicles selected from carriers,adjuvants and excipients. Suitable pharmaceutically acceptable vehiclesmay include, for example, inert solid diluents and fillers, diluents,including sterile aqueous solution and various organic solvents,permeation enhancers, solubilizers and adjuvants. Such compositions areprepared in a manner well known in the pharmaceutical art. See, e.g.,Remington's Pharmaceutical Sciences, Mace Publishing Co., Philadelphia,Pa. 17th Ed. (1985); and Modern Pharmaceutics, Marcel Dekker, Inc. 3rdEd. (G. S. Banker & C. T. Rhodes, Eds.). About 0.1% to about 90% of thetotal weight of the composition may be the active ingredient.

The therapeutic agents of the disclosure may be administered by the sameroute of administration or by different routes of administration. Insome embodiments, the cancer therapy is administered intravenously,intramuscularly, subcutaneously, topically, orally, transdermally,intraperitoneally, intraorbitally, by implantation, by inhalation,intrathecally, intraventricularly, or intranasally. In some embodiments,the antibiotic is administered intravenously, intramuscularly,subcutaneously, topically, orally, transdermally, intraperitoneally,intraorbitally, by implantation, by inhalation, intrathecally,intraventricularly, or intranasally. The appropriate dosage may bedetermined based on the type of disease to be treated, severity andcourse of the disease, the clinical condition of the individual, theindividual's clinical history and response to the treatment, and thediscretion of the attending physician.

One mode for administration is parenteral, for example, by injection.The forms in which the pharmaceutical compositions described herein maybe incorporated for administration by injection include, for example,aqueous or oil suspensions, or emulsions, with sesame oil, corn oil,cottonseed oil, or peanut oil, as well as elixirs, mannitol, dextrose,or a sterile aqueous solution, and similar pharmaceutical vehicles.

Oral administration may be another route for administration of thecompounds described herein. Administration may be via, for example,capsule or enteric coated tablets. In making the pharmaceuticalcompositions that include at least one compound described herein or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, the activeingredient is usually diluted by an excipient and/or enclosed withinsuch a carrier that can be in the form of a capsule, sachet, paper orother container. When the excipient serves as a diluent, it can be inthe form of a solid, semi-solid, or liquid material, which acts as avehicle, carrier or medium for the active ingredient. Thus, thecompositions can be in the form of tablets, pills, powders, lozenges,sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups,aerosols (as a solid or in a liquid medium), ointments containing, forexample, up to 10% by weight of the active compound, soft and hardgelatin capsules, sterile injectable solutions, and sterile packagedpowders.

Some examples of suitable excipients include, e.g., lactose, dextrose,sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate,alginates, tragacanth, gelatin, calcium silicate, microcrystallinecellulose, polyvinylpyrrolidone, cellulose, sterile water, syrup andmethyl cellulose. The formulations can additionally include lubricatingagents such as talc, magnesium stearate and mineral oil; wetting agents;emulsifying and suspending agents; preserving agents such as methyl andpropylhydroxy-benzoates; sweetening agents; and flavoring agents.

The compositions that include at least one compound described herein ora pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof can beformulated so as to provide quick, sustained or delayed release of theactive ingredient after administration to the subject by employingprocedures known in the art. Controlled release drug delivery systemsfor oral administration include osmotic pump systems and dissolutionalsystems containing polymer-coated reservoirs or drug-polymer matrixformulations. Another formulation for use in the methods disclosedherein employ transdermal delivery devices (“patches”). Such transdermalpatches may be used to provide continuous or discontinuous infusion ofthe compounds described herein in controlled amounts. The constructionand use of transdermal patches for the delivery of pharmaceutical agentsis well known in the art. Such patches may be constructed forcontinuous, pulsatile, or on demand delivery of pharmaceutical agents.

For preparing solid compositions such as tablets, the active ingredientmay be mixed with a pharmaceutical excipient to form a solidpreformulation composition containing a homogeneous mixture of acompound described herein or a pharmaceutically acceptable salt,isotopically enriched analog, stereoisomer, mixture of stereoisomers, ortautomer thereof. When referring to these preformulation compositions ashomogeneous, the active ingredient may be dispersed evenly throughoutthe composition so that the composition may be readily subdivided intoequally effective unit dosage forms such as tablets, pills and capsules.

The tablets or pills of the compounds described herein may be coated orotherwise compounded to provide a dosage form affording the advantage ofprolonged action, or to protect from the acid conditions of the stomach.For example, the tablet or pill can include an inner dosage and an outerdosage component, the latter being in the form of an envelope over theformer. The two components can be separated by an enteric layer thatserves to resist disintegration in the stomach and permit the innercomponent to pass intact into the duodenum or to be delayed in release.A variety of materials can be used for such enteric layers or coatings,such materials including a number of polymeric acids and mixtures ofpolymeric acids with such materials as shellac, cetyl alcohol andcellulose acetate.

Compositions for inhalation or insufflation may include solutions andsuspensions in pharmaceutically acceptable, aqueous or organic solvents,or mixtures thereof, and powders. The liquid or solid compositions maycontain suitable pharmaceutically acceptable excipients as describedherein. In some embodiments, the compositions are administered by theoral route, or by the nasal respiratory route for rapid delivery toblood/blood vessels via the lungs, for local and/or systemic effect. Inother embodiments, compositions in pharmaceutically acceptable solventsmay be nebulized by use of inert gases. Nebulized solutions may beinhaled directly from the nebulizing device or the nebulizing device maybe attached to a facemask tent, or intermittent positive pressurebreathing machine. Solution, suspension, or powder compositions may beadministered, preferably orally or nasally, from devices that deliverthe formulation in an appropriate manner.

6. Dosing

The specific dose level of a compound of the present application for anyparticular subject will depend upon a variety of factors including theactivity of the specific compound employed, the age, body weight,general health, sex, diet, time of administration, route ofadministration, and rate of excretion, drug combination and the severityof the particular disease in the subject undergoing therapy.

The treatments may include various “unit doses.” Unit dose is defined ascontaining a predetermined-quantity of the therapeutic composition. Thequantity to be administered, and the particular route and formulation,is within the skill of determination of those in the clinical arts. Aunit dose need not be administered as a single injection but maycomprise continuous infusion over a set period of time. In someembodiments, a unit dose comprises a single administrable dose.

The quantity to be administered, both according to number of treatmentsand unit dose, depends on the treatment effect desired. An effectivedose is understood to refer to an amount necessary to achieve aparticular effect. In the practice in certain embodiments, it iscontemplated that doses in the range from 10 mg/kg to 200 mg/kg canaffect the protective capability of these agents. Thus, it iscontemplated that doses include doses of about 0.1, 0.5, 1, 5, 10, 15,20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 105,110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175,180, 185, 190, 195, and 200, 300, 400, 500, 1000 μg/kg, mg/kg, μg/day,or mg/day or any range derivable therein. Furthermore, such doses can beadministered at multiple times during a day, and/or on multiple days,weeks, or months.

In certain embodiments, the effective dose of the pharmaceuticalcomposition is one which can provide a blood level of about 1 μM to 150μM. In another embodiment, the effective dose provides a blood level ofabout 4 μM to 100 μM.; or about 1 μM to 100 μM; or about 1 μM to 50 μM;or about 1 μM to 40 μM; or about 1 μM to 30 μM; or about 1 μM to 20 μM;or about 1 μM to 10 μM; or about 10 μM to 150 μM; or about 10 μM to 100μM; or about 10 μM to 50 μM; or about 25 μM to 150 μM; or about 25 μM to100 μM; or about 25 μM to 50 μM; or about 50 μM to 150 μM; or about 50μM to 100 μM (or any range derivable therein). In other embodiments, thedose can provide the following blood level of the agent that resultsfrom a therapeutic agent being administered to a subject: about, atleast about, or at most about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67,68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85,86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 μM or anyrange derivable therein. In certain embodiments, the therapeutic agentthat is administered to a subject is metabolized in the body to ametabolized therapeutic agent, in which case the blood levels may referto the amount of that agent. Alternatively, to the extent thetherapeutic agent is not metabolized by a subject, the blood levelsdiscussed herein may refer to the unmetabolized therapeutic agent.

For example, a dosage may be expressed as a number of milligrams of acompound described herein per kilogram of the subject's body weight(mg/kg). Dosages of between about 0.1 and 150 mg/kg may be appropriate.In some embodiments, about 0.1 and 100 mg/kg may be appropriate. Inother embodiments a dosage of between 0.5 and 60 mg/kg may beappropriate. In some embodiments, a dosage of from about 0.0001 to about100 mg per kg of body weight per day, from about 0.001 to about 50 mg ofcompound per kg of body weight, or from about 0.01 to about 10 mg ofcompound per kg of body weight may be appropriate. Normalizing accordingto the subject's body weight is particularly useful when adjustingdosages between subjects of widely disparate size, such as occurs whenusing the drug in both children and adult humans or when converting aneffective dosage in a non-human subject such as dog to a dosage suitablefor a human subject.

7. Synthesis of the Compounds

The compounds may be prepared using the methods disclosed herein androutine modifications thereof, which will be apparent given thedisclosure herein and methods well known in the art. Conventional andwell-known synthetic methods may be used in addition to the teachingsherein. The synthesis of typical compounds described herein may beaccomplished as described in the following examples. If available,reagents and starting materials may be purchased commercially, e.g.,from Sigma Aldrich or other chemical suppliers.

It will be appreciated that where specific process conditions (i.e.,reaction temperatures, times, mole ratios of reactants, solvents,pressures, etc.) are given, other process conditions can also be usedunless otherwise stated. Optimum reaction conditions may vary with theparticular reactants or solvent used, but such conditions can bedetermined by one skilled in the art by routine optimization procedures.

Additionally, conventional protecting groups may be necessary to preventcertain functional groups from undergoing undesired reactions. Suitableprotecting groups for various functional groups as well as suitableconditions for protecting and deprotecting particular functional groupsare well known in the art. For example, numerous protecting groups aredescribed in Wuts, P. G. M., Greene, T. W., & Greene, T. W. (2006).Greene's protective groups in organic synthesis. Hoboken, N.J.,Wiley-Interscience, and references cited therein.

Furthermore, the compounds of this disclosure may contain one or morechiral centers. Accordingly, if desired, such compounds can be preparedor isolated as pure stereoisomers, i.e., as individual enantiomers ordiastereomers or as stereoisomer-enriched mixtures. All suchstereoisomers (and enriched mixtures) are included within the scope ofthis disclosure, unless otherwise indicated. Pure stereoisomers (orenriched mixtures) may be prepared using, for example, optically activestarting materials or stereoselective reagents well-known in the art.Alternatively, racemic mixtures of such compounds can be separatedusing, for example, chiral column chromatography, chiral resolvingagents, and the like.

The starting materials for the following reactions are generally knowncompounds or can be prepared by known procedures or obviousmodifications thereof. For example, many of the starting materials areavailable from commercial suppliers such as Aldrich Chemical Co.(Milwaukee, Wis., USA), Bachem (Torrance, Calif., USA), Emka-Chemce orSigma (St. Louis, Mo., USA). Others may be prepared by procedures orobvious modifications thereof, described in standard reference textssuch as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-15(John Wiley, and Sons, 1991), Rodd's Chemistry of Carbon Compounds,Volumes 1-5, and Supplementals (Elsevier Science Publishers, 1989)organic Reactions, Volumes 1-40 (John Wiley, and Sons, 1991), March'sAdvanced Organic Chemistry, (John Wiley, and Sons, 5th Edition, 2001),and Larock's Comprehensive Organic Transformations (VCH Publishers Inc.,1989).

General Synthesis

In certain embodiments, provided is a method of preparing a compound ofFormula (I):

wherein R¹, R², R⁵, R⁶, R⁷, R⁸, R⁹ and n are as described herein.

In certain embodiments, the method comprises contacting R¹—H, optionallyin the presence of a base, with a compound of Formula (I-A):

wherein Lg is a leaving group, such as halo, e.g., Cl or Br, to form thecompound of Formula (I) or a pharmaceutically acceptable salt,isotopically enriched analog, stereoisomer, mixture of stereoisomers, ortautomer thereof.

In certain embodiments, the compound of Formula (I-A) is prepared by amethod comprising converting a compound of Formula (I-B) to the compoundof Formula (I-A)

In certain embodiments, the compound of Formula (I-B) is prepared by amethod comprising cyclizing a compound of Formula (I-C) (wherein R⁴¹ isa C₁₋₄ alkyl) to the compound of Formula (I-B)

In certain embodiments, the compound of Formula (I-C) is prepared by amethod comprising contacting an optionally substituted aniline ofFormula (I-D) with a compound of Formula (I-E) (wherein R⁴² is a C₁₋₄alkyl) to form the compound of Formula (I-C)

In certain embodiments, the compound of Formula (I-E) is prepared by amethod comprising contacting trialkyl orthoformate with a compound ofFormula (I-F)

Scheme I illustrates a general method which can be employed for thesynthesis of compounds described herein.

Referring to Scheme I, wherein R¹, R², R⁵, R⁶, R⁷, R⁸, R⁹ and n are asdescribed herein, appropriate starting materials and reagents, such ascompound I-1, can be purchased or prepared by methods known to one ofskill in the art or by methods described herein, such as in Scheme II.

Step I-1: Compound I-1 reacts with a sodium salt (e.g., Na₂SO₃) or asodium base (e.g., NaHCO₃), or a mixture thereof in an aqueous solutionto give Compound I-2. The reaction can be carried out under heatingconditions, such as at a temperature of from about 60° C. to about 100°C. Examples of the reaction are illustrated in Example 1, Step 1-2, andExample 6, Step 6-2.

Step I-2: Compound I-2 reacts with Lg¹-CH₂C(O)OCH₃, wherein Lg¹ is aleaving group, such as Cl or Br, to provide 1-3. The reaction can becarried out in a solvent, such as DMF, under heating conditions, such asat a temperature of from about 60° C. to about 100° C. An example of thereaction is illustrated in Example 1, Step I-3.

Step I-3: Compound I-3 reacts with triethyl orthoformate and aceticanhydride to provide Compound I-4. The reaction can be carried out underreflex conditions. An example of the reaction is illustrated in Example1, Step I-4.

Step I-4: Compound I-4 reacts with amino Compound I-5 to provideCompound I-6. The reaction can be carried out in a solvent, such asdiphenyl ether, under heating conditions, such as at a temperature offrom about 100° C. to about 150° C. Compound I-6 then cyclizes toCompound I-7. The cyclization reaction can be carried out in a solvent,such as diphenyl ether, under reflux conditions. An example of thereaction is illustrated in Example 1, Step I-5.

Step I-5: Compound I-7 reacts with POCl₃ to give Compound I-8. Thereaction can be carried out under reflux conditions. Optionally, asolvent, such as DMF, may be used. Examples of the reaction areillustrated in Example 1, Step I-6, and Example 3.

Step I-5A: When R⁶ of Compound I-8 is —SR¹⁶ (wherein R¹⁶ is as definedherein), the —SR¹⁶ group can be oxidized to —S(O)R¹⁶ using 1 eq. of anoxidizing reagent, such as mCPBA, to give Compound I-8 wherein R⁶ is—S(O)R¹⁶. The reaction can be carried out at a low temperature of below0° C., such as about −20° C. An example of the reaction is illustratedin Example 8, Step 8-1.

Step I-5B: When R⁶ of Compound I-8 is —SR¹⁶ (wherein R¹⁶ is as definedherein), the —SR¹⁶ group can be oxidized to —S(O)₂R¹⁶ by adding anexcess amount of an oxidizing reagent, such as 2. eq. of mCPBA, to giveCompound I-8 wherein R⁶ is —S(O)₂R¹⁶. The reaction can be carried out ata temperature of about 0° C. An example of the reaction is illustratedin Example 9.

Step I-6: Compound I-8 reacts with Compound R1-H to give Compound I-9.The reaction can be carried out in a solvent, such as 1,4-dioxane andDMF, optionally with heating, such as at a temperature of about 30° C.to reflex. In certain embodiments, a base such as NaH can be added todeprotonate Compound R¹—H before reaction with Compound I-8. Examples of1-6 are illustrated in Example 1, Step 1-7 (I-6A), Example 2 (I-6B), andExample 5 (I-6C).

Step I-7: When R⁶ of Compound I-9 is an ester —C(O)OR¹⁵ (wherein R¹⁵ isas defined herein but is not H), —C(O)OR¹⁵ can be hydrolyzed to —C(O)OHwith a base such as LiOH, in an aqueous solution, to give Compound I-9wherein R⁶ is —C(O)OH. An example of the reaction is illustrated inExample 3, conversion of Compound 63 to Compound 66. Similarly, an estergroup at other positions of a compound can be hydrolyzed to an acidgroup.

Step I-8: Compound I-9 wherein R⁶ is —C(O)OH can be converted toCompound I-9 wherein R⁶ is —C(O)NR¹⁵R¹⁵ by reacting with an amineHNR¹⁵R¹⁵ under amide coupling reaction conditions. Amide couplingreaction conditions can include a solvent, such as NMP, DMF, DCM, acoupling reagent, such as EDCI, optionally an additional agent, such asHOBt, and optionally a base, such as triethylamine. The reaction can becarried out at about 0° C. to room temperature. An example of thereaction is illustrated in Example 7.

Scheme II shows a method of preparing starting material I-1 used inScheme I from compound II-1.

In certain embodiments, Compound II-1 reacts with phosphorus oxychlorideand concentrated sulfuric acid to give Compound I-1 (II-A). The reactionmay be carried out at an elevated temperature, such as about 60° C. toabout 100° C. An example of the reaction is illustrated in Example 1,Step I-1.

In certain embodiments, Compound II-1 reacts with chlorosulfonic acid togive Compound I-1 (II-B). The reaction may be carried out at a lowtemperature, such as about −10° C. to about 10° C. An example of thereaction is illustrated in Example 6, Step 6-1.

Scheme III shows a method of preparing starting material II-1. PhenolCompound II-1 react with Lg²-R¹⁸ to give Compound II-2, wherein R² is—OR¹⁸, R⁹ and R¹⁸ are as defined herein, and Lg² is a leaving group,such as a halo. The reaction can be carried out in a solvent, such asacetone in the presence of a base such as K₂CO₃, and a phase transfercatalyst, such as tetra-n-butylammonium iodide. An example of thereaction is illustrated in Example 10.

Scheme IV shows a method of preparing Intermediates such as IV-13,IV-14, and IV-15, wherein R², R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁵, R¹⁶, and n are asdefined herein. An example of the method is illustrated in Example 18.

Scheme IA illustrates a general method which can be employed for thesynthesis of compounds described herein.

Referring to Scheme IA, wherein R¹, R²¹¹, R⁶, R⁹¹, and R⁹² are asdescribed herein, appropriate starting materials and reagents, such ascompound I-1, can be purchased or prepared by methods known to one ofskill in the art or by methods described herein, such as in Scheme IIA.

Step I-1: Compound I-1 reacts with a sodium salt (e.g., Na₂SO₃) or asodium base (e.g., NaHCO₃), or a mixture thereof in an aqueous solutionto give Compound I-2. The reaction can be carried out under heatingconditions, such as at a temperature of from about 60° C. to about 100°C.

Step I-2: Compound I-2 reacts with LG¹-CH₂C(O)OCH₃, wherein Lg1 is aleaving group, such as Cl or Br, to provide 1-3. The reaction can becarried out in a solvent, such as DMF, under heating conditions, such asat a temperature of from about 60° C. to about 100° C.

Step I-3: Compound I-3 reacts with triethyl orthoformate and aceticanhydride to provide Compound I-4. The reaction can be carried out underreflex conditions.

Step I-4: Compound I-4 reacts with amino Compound I-5 to provideCompound I-6. The reaction can be carried out in a solvent, such asdiphenyl ether, under heating conditions, such as at a temperature offrom about 100° C. to about 150° C. Compound I-6 then cyclizes toCompound I-7. The cyclization reaction can be carried out in a solvent,such as diphenyl ether, under reflux conditions.

Step I-5: Compound I-7 reacts with POCl₃ to give Compound I-8. Thereaction can be carried out under reflux conditions. Optionally, asolvent, such as DMF, may be used.

Step I-5A: When R⁶ of Compound I-8 is —SR¹⁶ (wherein R¹⁶ is alkyl), the—SR¹⁶ group can be oxidized to —S(O)R¹⁶ using 1 eq. of an oxidizingreagent, such as mCPBA, to give Compound I-8 wherein R⁶ is —S(O)R¹⁶. Thereaction can be carried out at a low temperature of below 0° C., such asabout −20° C.

Step I-5B: When R⁶ of Compound I-8 is —SR¹⁶ (wherein R¹⁶ is alkyl), the—SR¹⁶ group can be oxidized to —S(O)₂R¹⁶ by adding an excess amount ofan oxidizing reagent, such as 2. eq. of mCPBA, to give Compound I-8wherein R⁶ is —S(O)₂R¹⁶. The reaction can be carried out at atemperature of about 0° C.

Step I-6: Compound I-8 reacts with Compound R¹—H to give Compound I-9.The reaction can be carried out in a solvent, such as 1,4-dioxane andDMF, optionally with heating, such as at a temperature of about 30° C.to reflex. In certain embodiments, a base such as NaH can be added todeprotonate Compound R¹—H before reaction with Compound I-8.

Step I-7: When R⁶ of Compound I-9 is an ester —C(O)OR¹⁵ (wherein R¹⁵ isalkyl), —C(O)OR¹⁵ can be hydrolyzed to —C(O)OH with a base such as LiOH,in an aqueous solution, to give Compound I-9 wherein R⁶ is —C(O)OH.

Step I-8: Compound I-9 wherein R⁶ is —C(O)OH can be converted toCompound I-9 wherein R⁶ is —C(O)NR¹⁵R¹⁵ by reacting with an amineHNR¹⁵R¹⁵ (each R¹⁵ is independently selected from H, alkyl, —CH₂CH₂NEt₂,—CH₂CH₂OH and heterocyclyl) under amide coupling reaction conditions.Amide coupling reaction conditions can include a solvent, such as NMP,DMF, DCM, a coupling reagent, such as EDCI, optionally an additionalagent, such as HOBt, and optionally a base, such as triethylamine. Thereaction can be carried out at about 0° C. to room temperature.

Scheme IIA shows a method of preparing starting material I-1 used inScheme IA from compound II-1.

In certain embodiments, Compound II-1 reacts with phosphorus oxychlorideand concentrated sulfuric acid to give Compound I-1 (II-A). The reactionmay be carried out at an elevated temperature, such as about 60° C. toabout 100° C.

In certain embodiments, Compound II-1 reacts with chlorosulfonic acid togive Compound I-1 (II-B). The reaction may be carried out at a lowtemperature, such as about −10° C. to about 10° C.

Scheme IIIA shows a method of preparing starting material II-1. PhenolCompound II-1 reacts with LG²-R¹⁸ to give Compound II-2, wherein R¹⁸ isselected from C₁₋₆ alkyl, C₁₋₆ haloalkyl, and C₁₋₆ aminoalkyl, and R²¹¹,R⁹¹ and R⁹² are as defined herein, and LG² is a leaving group, such as ahalo. The reaction can be carried out in a solvent, such as acetone inthe presence of a base such as K₂CO₃, and a phase transfer catalyst,such as tetra-n-butylammonium iodide.

Scheme IVA shows a method of preparing Intermediates such as IV-13,IV-14, and IV-15, wherein R²¹¹, R⁹¹, R⁹², R¹⁵, and R¹⁶, are as definedherein.

For any of the preceding schemes, a poly(ethylene glycol) group or amethoxypoly(ethylene glycol) group can be attached to any compounddescribed herein via the terminal hydroxy group of PEG or mPEG, and byany suitable poly-ol conjugation reaction (e.g., Mitsunobu ethersynthesis, halogen displacement, ester formation, and the like).

EXAMPLES

The following examples are included to demonstrate specific embodimentsof the disclosure. It should be appreciated by those of skill in the artthat the techniques disclosed in the examples which follow representtechniques to function well in the practice of the disclosure, and thuscan be considered to constitute specific modes for its practice.However, those of skill in the art should, in light of the presentdisclosure, appreciate that many changes can be made in the specificembodiments which are disclosed and still obtain a like or similarresult without departing from the spirit and scope of the disclosure.

SYNTHETIC EXAMPLES Example 1. Synthesis of Compound 1 Step I-1

To a solution of ethylbenzene (96.5 g, 0.91 mol, 1.3 eq.) was addedphosphorus oxychloride (65 mL, 0.7 mol, 1.0 eq.) at 70° C. Afterstirring for 20 min at this temperature, concentrated sulfuric acid (48mL, 0.91 mol, 1.0 eq.) was added dropwise into the mixture. Theresulting solution was then incrementally heated to 80° C. for 2 hours,then to 90° C. for 3 hours. After cooling to room temperature, themixture was washed twice with ice water (2×200 mL). The organic extractwas separated and concentrated under reduced pressure to obtain 150 g(81%) of the crude product. The crude product as oil was used withoutfurther purification.

Step I-2

To a mixture of Na₂SO₃ (173 g, 1.37 mol, 1.87 eq.) and NaHCO₃ (121 g,1.44 mol, 1.96 eq.) in H₂O (700 mL) was added portion-wise4-ethylbenzenesulfonyl chloride (150 g, 0.73 mol, 1 eq.) at 75° C.

After addition, the reaction mixture was kept at this temperature for 1hour before cooling. The crude product was washed with t-butyl methylether, dried (75 g, 53%) and used without further purification.

Step I-3

To a mixture of sodium 4-ethylbenzenesulfinate (5 g, 26 mmol, 1.1 eq.)in DMF (22 mL) was added methyl 2-bromoacetate (2.3 mL, 24 mmol, 1 eq.)at room temperature. The resulting mixture was heated to 80° C. and keptthis temperature with stirring for 2 hours. After cooling to roomtemperature, the mixture was diluted with water (44 mL). The aqueouslayer was extracted with CH₂Cl₂ (2×25 mL). The combined organic extractswere washed with water 4 times (4×20 mL) to remove DMF, dried andconcentrated under reduced pressure. The crude product as oil (5.3 g,92%) was used without further purification.

Step I-4

The mixture of crude methyl 2-((4-ethylphenyl)sulfonyl)acetate (23.6 g,97 mmol, 1.0 eq.), triethyl orthoformate (39 mL, 233 mmol, 2.4 eq.) andacetic anhydride (20 mL, 214 mmol, 2.21 eq.) was reflux for 3 hours withsimultaneous distillation of ethyl acetate, triethyl orthoformate andacetic anhydride and then evaporated to dryness. The crude product asoil (23.7 g, 82%) was used for the next step without purification: ¹HNMR(600 MHz, CDCl₃, 25° C.): 1.25 (t, 3H, J=7.8 Hz), 1.44 (t, 3H, J=7.2Hz), 2.71 (q, 2H, J=7.8 Hz), 3.70 (s, 3H), 4.36 (q, 2H, J=7.2 Hz),7.31-7.33 (m, 2H), 7.83-7.85 (m, 2H), 8.13 (s, 1H).

Step I-5

The mixture of crude ethyl(E)-3-ethoxy-2-((4-ethylphenyl)sulfonyl)acrylate (87.6 g, 0.29 mol, 1eq.) and 4-(trifluoromethoxy)-aniline (39 mL, 0.29 mol, 1.0 eq.) indiphenyl ether (120 mL) was heated at 130° C. for 4 hours. After coolingto room temperature, the product was collected by filtration or purifiedby flash chromatography (EtOAc:Petroleum ether; 1:5) to affordIntermediate 1-6 (74.6 g, 59%) as white solid.

The Intermediate 1-6 (31.3 g, 0.17 mol) in diphenyl ether (180 mL) washeated at reflux for 4 hours before cooling to room temperature to giveIntermediate 1-7. The solid was collected by filtration, dried (27 g,55%) and used without further purification.

Step I-6

A mixture of 3-((R1-)sulfonyl)-6-(R2-)quinolin-4-ol (Intermediate 1-7)(8 g, 20 mmol) and POCl₃ (50 mL) was heated to reflux until all thestart material was consumed (˜3 hours). The resulting mixture wasconcentrated to followed by the addition of CH₂Cl₂ (100 mL) and icewater (100 mL). The organic phase was adjusted to pH 9˜10 by using 25%NH₃.H₂O. The organic phase was then separated, concentrated and purifiedby flash chromatography (EtOAc:Petroleum ether; 1:5) to afford 8.1 g(97%) of the desired Intermediate 1-8 as white solid: ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.27 (t, 3H, J=7.8 Hz), 2.74 (q, 2H, J=7.8 Hz), 7.39 (d,2H, J=8.4 Hz), 7.77 (dd, 1H, J=6.6, 2.4 Hz), 7.97-7.99 (m, 2H), 8.16 (s,1H), 8.28 (d, 1H, J=9 Hz), 9.66 (s, 1H).

Step I-7

A solution of Intermediate 1-8 (800 mg, 1.9 mmol, 1.0 eq.) and1-methylpiperazine (213 μL, 4.2 mmol, 2.2 eq.) in CH₃CN (20 mL) washeated to 45° C. and kept at this temperature with stirring for 4 hours(until all the start material was consumed). The mixture was thenconcentrated under reduced pressure and purified by flash chromatography(EtOAc:Petroleum ether; 1:2) to afford the desired Compound 1 (801 mg,89%) as a light yellow solid: ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (t,3H, J=7.8 Hz), 2.37 (s, 3H), 2.42 (m, 4H), 2.73 (q, 2H, J=9 Hz), 3.29(m, 4H), 5.25 (s, 2H), 7.34 (d, 2H, J=8.4 Hz), 7.67 (dd, 1H, J=9, 1.8Hz), 7.78 (d, 2H, J=7.8 Hz), 8.10 (s, 1H), 8.22 (d, 1H, J=9.6 Hz), 9.41(s, 1H). MS (m/z): 480.

Example 2. Synthesis of Compound 51

A solution of Intermediate 1-8 (300 mg, 0.72 mmol, 1.0 eq.) and1H-1,2,4-triazole (55 mg, 0.79 mmol, 1.1 eq.) in 1,4-dioxane (9 mL) washeated to reflux for 24 hours (until all the start material wasconsumed). The mixture was then concentrated under reduced pressure andpurified by flash chromatography (EtOAc:Petroleum ether; 1:5) to affordCompound 51 (270 mg, 84%) as a while solid: ¹HNMR (600 MHz, D6-DMSO, 25°C.): 1.20 (t, 3H, J=7.8 Hz), 2.65 (q, 2H, J=15.6 Hz), 6.96 (m, 1H), 7.23(d, 2H, J=8.4 Hz), 7.41 (d, 2H, J=8.4 Hz), 7.75 (dd, 1H, J=9, 1.8 Hz),8.0 (s, 1H), 8.32 (d, 1H, J=9 Hz), 8.65 (s, 1H), 9.78 (s, 1H).

Example 3. Synthesis of Compound 63 and Compound 66

Ethyl 3-((4-ethylphenyl)sulfonyl)-4-hydroxyquinoline-6-carboxylate(Intermediate 3-1) was prepared from Intermediate 1-5 and ethyl4-aminobenzoate according to a procedure similar to that described inExample 1, Step 6.

A mixture ethyl3-((4-ethylphenyl)sulfonyl)-4-hydroxyquinoline-6-carboxylate (2 g, 5.2mmol) and POCl₃ (2.9 mL, 31 mmol, 6 eq.) in DMF (40 mL) was heated toreflux until all the start material was consumed (˜3 hours). Aftercooling, the resulting mixture was quenched by addition of 70 mL of icewater. The organic phase was adjusted to pH 9−10 by using 25% NH₃.H₂O.The organic phase was then separated, concentrated and purified by flashchromatography (EtOAc:Petroleum ether; 1:5) to afford 1.5 g (71%) ofIntermediate 3-2 as a white solid.

Compound 63 was prepared using Intermediate 3-2 according to a proceduresimilar to that described in Example 1 (Step I-1 to 1-7).

To a solution of Compound 63 (720 mg, 1.5 mmol) in MeOH (60 mL) wasadded LiOH.H₂O (126 mg, 3 mmol, 2.0 eq.) in water (2 mL). After theresulting solution was heated to 45° C. and stirred the same temperaturefor 5 hours, the pH was adjusted to 5-6 by using 2N HCl solution. Theproduct was filtered, concentrated under reduced pressure and purifiedby flash chromatograph (CH₂Cl₂:MeOH; 1:3) to afford Compound 66 (640 mg,94%) as a yellow solid: ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.17 (t, 3H,J=7.8 Hz), 2.07 (m, 2H), 2.64 (s, 3H), 2.70 (q, 2H, J=15 Hz), 3.13 (m,8H), 7.15 (d, 2H, J=8.4 Hz), 7.87 (d, 2H, J=8.4 Hz), 8.18 (d, 1H, J=8.4Hz), 8.38 (dd, 1H, J=9, 1.2 Hz), 8.75 (s, 1H), 9.36 (s, 1H).

Example 4. Synthesis of Compound 102 Synthesis of Intermediate 4-4

Titanium(IV) isopropoxide (36.2 g, 127 mmol) was added dropwise to asolution of amine 4-2 (7.7 g, 76.4 mmol) in 130 mL of MeOH. It was thenfollowed by the addition of ketone 4-1 (12.7 g, 63.7 mmol). The reactionmixture was stirred at room temperature for 5 hours, followed byaddition of sodium borohydride (2.4 g, 63.7 mmol). After additional 2hours of stirring, the resulting mixture was quenched by water (13 mL).Inorganic precipitate was filtered and washed with ethyl acetate. Thecombined organic phases were concentrated under reduced pressure and theresidue was purified by column chromatography on silica gel (petroleumether/ethyl acetate=1:1) to give BOC-protected compound 4-3 as paleyellow oil (12 g, 67%).

A solution of BOC-protected compound 4-3 (8 g, 28 mmol) in 50 mL ofethanol was added dropwise to HCl/EtOH (4M, 100 mL) at room temperaturewhile stirring. After 4 hours, the solvent was evaporated, and remainingresidue was redissolved by using a mixture of 20 mL of MeOH and 100 mLof CH₂Cl₂, followed by the addition of 5 g of K₂CO₃. The resultingmixture was filtered through a pad of Celite after 16 hours of stirring.The filtrate was concentrate under reduced pressure to give Intermediate4-4 as brown oil (5 g, 97%).

Synthesis of Compound 102

Compound 102 was prepared from Intermediates 1-8 and 4-4 according to amethod similar to that described in Step I-8 of Example 1.

Example 5. Synthesis of Compound 108

To a slurry of NaH (43 mg, 60% in mineral oil, 1.08 mmol, 1.5 eq.) inDMF (13 mL) was added 1H-pyrrole (60 μL, 0.86 mmol, 1.2 eq.) at roomtemperature. After 30 min, Intermediate 1-8 (300 mg, 0.72 mmol, 1.0 eq.)was added to the mixture and the resulting reaction was heated at 45° C.for 4 hours (until all the start material was consumed). After coolingto room temperature, the reaction mixture was diluted with water (39 mL)and CH₂Cl₂. The organic extracts was then concentrated and purified byflash chromatography (EtOAc:Petroleum ether; 1:5) to afford Compound 108(40 mg, 12%) as a while solid: ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.19 (t,3H, J=7.8 Hz), 2.63 (q, 2H, J=15 Hz), 6.33 (m, 2H), 6.53 (m, 2H), 6.87(m, 1H), 7.15 (d, 2H, J=8.4 Hz), 7.39 (d, 2H, J=7.8 Hz), 7.68 (d, 1H,J=7.8 Hz), 8.26 (d, 1H, J=9 Hz), 9.78 (s, 1H).

Example 6. Synthesis of Compound 144

Step 6-1

To a solution of anisole (10 g, 93 mmol, 1.0 eq.) in CH₂Cl₂ (50 mL) wasadded dropwise chlorosulfonic acid (12.3 mL, 185 mmol, 2 eq.) in CH₂Cl₂(10 mL) between 0° C. and 10° C. The resulting mixture was washed twicewith water (2×100 mL). The organic extract was separated andconcentrated under reduced pressure. The crude product was purified byflash chromatograph (EtOAc:Petroleum ether; 1:10) to afford (10.6 g,56%) of 4-methoxybenzenesulfonyl chloride as a white solid.

Step 6-2

To a mixture of Na₂SO₃ (7.2 g, 57 mmol, 1.87 eq.) and NaHCO₃ (5.1 g, 61mmol, 1.96 eq.) in H₂O (60 mL) was added portion-wise4-methoxybenzenesulfonyl chloride (6.32 g, 31 mmol, 1 eq.) at 75° C.After addition, the reaction mixture was kept at this temperature for 1hour before cooling. 20 mL of EtOH was then added followed by filtrationto remove all inorganic salts. The crude organic phase was concentratedunder reduced pressure to give Intermediate 6-1 which was used withoutfurther purification.

Compound 144 was prepared using Intermediate 6-1 according to aprocedure similar to that described in Example 1 and Example 3 toprepare Compound 63.

Example 7. Synthesis of Compound 165

Intermediate 7-1 (300 mg, 0.66 mmol, prepared from Compound 144according to a procedure similar to that described in Example 3 toprepare Compound 66) in NMP (12 mL) was added sequentially HOBt (101 mg,0.66 mmol, 1.5 eq.), EDCI (102 mg, 0.66 mmol, 1.5 eq.), triethylamine(184 μL, 1.32 mmol, 3.0 eq.) then finally diethylamine (136 μL, 1.32mmol, 2.0 eq.) at room temperature. After stirring for overnight, thereaction mixture was quenched by water and extracted by CH₂Cl₂, purifiedby flash chromatography (CH₂Cl₂:MeOH; 1:3) to afford Compound 165 (50mg, 22%) as a yellow solid: ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (m,6H), 2.04 (m, 4H), 2.56 (s, 3H), 2.93 (m, 2H), 3.43 (m, 8H), 3.89 (s,3H), 7.03 (d, 2H, J=7.8 Hz), 7.77 (dd, 1H, J=8.4, 1.8 Hz), 7.87 (d, 2H,J=9 Hz), 8.16 (d, 1H, J=9 Hz), 8.22 (m, 1H), 9.08 (s, 1H).

Example 8. Synthesis of Compound 168

Step 8-1

To a solution of Intermediate 8-1 (200 mg, 0.47 mmol, prepared accordingto a method similar to that described in Example 1) in CH₂Cl₂ (20 mL)was added mCPBA (82 mg, 0.47 mmol, 1.0 eq.) at −20° C. The reaction wasslowly warmed to room temperature over 0.5 hours. The reaction wasquenched with Na₂CO₃/H₂O. The organic extract was separated and purifiedby flash chromatograph (100% EtOAc) to afford Intermediate 9-2 (200 mg,97%) as white solid.

Step 8-2

Compound 168 was prepared from Intermediates 8-2 and 4-4 according to aprocedure similar to that described in Example 1, Step I-7.

Example 9. Synthesis of Compound 169

To a solution of Intermediate 8-2 (200 mg, 0.47 mmol) in CH₂Cl₂ (20 mL)was added mCPBA (164 mg, 0.94 mmol, 2.0 eq.) at 0° C. The reaction wasslowly warmed to room temperature over 0.5 hours. The reaction wasquenched with Na₂CO₃/H₂O. The organic extract was separated and purifiedby flash chromatograph (EtOAc:Petroleum ether; 1:2) to affordIntermediate 9-1 (120 mg, 56%) as white solid.

Compound 168 was prepared from Intermediate 10-1 and 1,4′-bipiperidineaccording to a procedure similar to that described in Example 1, StepI-7.

Example 10. Synthesis of Compound 218

To a solution of phenol (111 g, 1.18 mol, 1.05 eq.) in acetone (1300 mL)was added 1-bromoheptane (200 g, 1.12 mol, 1.0 eq.), K₂CO₃ (307 g, 2.2mol, 2 eq.), and tetra-n-butylammonium iodide (2 g, 5 mmol, 0.5%) atroom temperature. The resulting mixture was heated to 60° C. and kept atthis temperature with stirring for 26 h. After cooling, the reaction wasfiltered and the solid wash with acetone (600 mL). The combined organicphases were concentrated to dryness, redissolved in CH₂Cl₂ (500 mL),washed with 2N sodium hydroxide solution (200 mL), the water (3*200 mL)before concentrated under reduced pressure. The crude product(heptyloxy)benzene (207 g, 97%) as a colorless oil, was used for thenext step without any purification.

Compound 218 was prepared from (heptyloxy)benzene according to a methodsimilar to that described in Step I-8 of Example 1.

Example 11. Synthesis of Compound 242

To a mixture of NaH (0.04 g, 0.974 mmol, 1.5 eq) in 16 mL of DMF wasadded 2-(diethylamino)ethan-1-ol (0.1 g, 0.844 mmol, 1.3 eq). Afterstirring at rt for 15 minutes, chloride starting material (0.3 g, 0.649mmol, 1 eq) was added to the mixture and resulting reaction was heatedto 65° C. and kept at the same temperature for 16 hours with stirring.After cooling to room temperature, the reaction was concentrated andresidues purified by flash chromatography (DCM:MeOH=10:1) that affordedCompound 242 (0.05 g, 14%) as yellow solid.

Example 12. Synthesis of Intermediate 12-4 Useful in Preparing CompoundsDescribed Herein Such as Compound 250

Preparation of Intermediate 12-3

Titanium(IV) isopropoxide (11.4 g, 40 mmol) was added dropwise to asolution of amine 12-2 (2.86 g, 22 mmol) in 40 mL of MeOH, followed bythe addition of ketone 12-1 (4.0 g, 20 mmol). The reaction mixture wasstirred at rt for 5 hours, then followed by addition of sodiumborohydride (0.76 g, 20 mmol) at 0° C. After 2 hours of additionalstirring at 0° C., the resulting mixture was quenched by water (4 mL).Inorganic precipitate was filtered and washed with ethyl acetate. Thecombined organic phases were concentrated under reduced pressure and theresidue was purified by column chromatography on silica gel (petroleumether/ethyl acetate=1:1) to give BOC-protected Intermediate 12-3 as paleyellow oil (3.6 g, 57%).

Preparation of Intermediate 12-4

A solution of Boc-protected Intermediate 12-3 (3.6 g, 11.5 mmol) in 20mL of methanol was added dropwise to HCl/EtOH (4M, 40 mL) at rt. After 4hours of stirring at rt, reaction was concentrated and remaining residuewas redissolved in a mixture of 10 mL of MeOH and 50 mL of CH₂Cl₂,followed by the addition of 5 g of K₂CO₃. After 16 hours of stirring,the resulting mixture was filtered through a pad of Celite. The filtratewas concentrate under reduced pressure to give Intermediate 12-4 as paleyellow solid (2.4 g, 100%).

Example 13. Synthesis of Compound 271

Compound 250 (0.1 g, 0.156 mmol, prepared according to a proceduresimilar to those described herein using Intermediate 12-4) was dissolvedby 9 ml of DMF followed by addition of mPEG-NHS (0.35 g, ˜0.156 mmol,obtained from NOF America Corporation (Catalog #: SUNBRIGHT® ME-020AS))at rt. After stirring at rt for 8 hours, the reaction mixture wasconcentrated to dryness, followed by purification using flashchromatography (DCM:MeOH=10:1). The crude product (Compound 271, 0.1 g,22%) was obtained as yellow solid.

Example 14. Synthesis of Intermediate 14-2 Useful in Preparing CompoundsDescribed Herein Such as Compound 292

Preparation of Intermediate 14-1

After stirring a mixture of Intermediate 12-4 (1.5 g, 7 mmol), ketone12-1 (2.8 g, 14 mmol) and AcOH (2 mL) in 30 mL of methanol was stirredat rt for 1 hour, NaBH₃CN (1.32 g, 21 mmol) was added. The resultingmixture was stirred at 60° C. After 7 hours, the reaction was cooled toambient temperature, followed by the addition of additional ketone 12-1(2.8 g, 14 mmol). After another 1 hour of stirring at rt, additionalNaBH₃CN (1.32 g, 21 mmol) was added. After stirring at 60° C. foranother 7 hours, the resulting mixture was concentrated and purified bycolumn chromatography on silica gel (petroleum ether/ethyl acetate=1:2,ethyl acetate/methanol=10:1 to 3:1) to give BOC-protected Intermediate14-1 as pale yellow solid (1.5 g, 54%).

Preparation of Intermediate 14-2

A solution of Boc-protected Intermediate 14-1 (1.5 g, 3.8 mmol) in 15 mLof methanol was added dropwise to HCl/EtOH (4M, 30 mL) at rt. Afterstirring at rt for 4 hours, the reaction was concentrated, and remainingresidue was redissolved by in a mixture of 10 mL of MeOH and 50 mL ofCH₂Cl₂, followed by the addition of 2 g of K₂CO₃. The resulting mixturewas filtered through a pad of Celite after 16 hours of stirring,concentrate under reduced pressure to give Intermediate 14-2 as paleyellow solid (1 g, 90%).

Example 15. Synthesis of Intermediates 15-4 and 15-2 Useful in PreparingCompounds Described Herein Such as Compounds 276 and 281

Preparation of Intermediate 15-2

To a solution of 1-Boc-piperazine (4 g, 21.5 mmol) in DMF (60 mL) wasadded NaH (3.44 g, 86 mmol) portion-wise at 5° C. The suspension wassubsequently heated to 50° C. After stirring at 50° C. for 5 hours, thereaction mixture was cooled to 5° C., followed by the addition of aminechloride (CAS #: 2008-75-5) (5.6 g, 30 mmol). After stirring at ambienttemperature for 16 hours, the reaction was quenched with water (60 mL)and extracted by ethyl acetate (3×50 mL). The organic layers werecollected, concentrated and purified by column chromatography on silicagel (petroleum ether/ethyl acetate=1:1 to ethyl acetate) to giveBoc-protected Intermediate 15-1 as yellow oil (4.3 g, 67%).

A solution of Boc-protected Intermediate 15-1 (4.3 g, 14.5 mmol) in 20mL of methanol was added dropwise HCl/EtOH (4M, 50 mL) at rt. After 4hours of stirring at rt, the reaction mixture was concentrated, and theremaining residue was redissolved by using a mixture of 10 mL of MeOHand 50 mL of CH₂Cl₂, followed by the addition of 6 g of K₂CO₃. Theresulting mixture was filtered through a pad of Celite after 16 hours ofstirring. The filtrate was concentrate under reduced pressure to givecrude Intermediate 15-2 as pale yellow solid (2.8 g, 100%).

Preparation of Intermediate 15-4

To a solution of 1-Boc-piperazine (4 g, 21.5 mmol) in DMF (60 mL) wasadded NaH (3.44 g, 86 mmol) portion-wise at 5° C. The suspension wassubsequently heated to 50° C. After stirring at 50° C. for 5 hours, thereaction mixture was cooled to 5° C., followed by the addition of aminechloride (CAS #: 7250-67-1) (5.5 g, 32.2 mmol). After stirring atambient temperature for 16 hour, the reaction was quenched with water(60 mL) and extracted by ethyl acetate (3×50 mL). The organic layerswere collected, concentrated and purified by column chromatography onsilica gel (petroleum ether/ethyl acetate=1:1 to ethyl acetate) to giveBoc-protected Intermediate 15-3 as yellow oil (2.6 g, 43%).

A solution of Boc-protected Intermediate 15-3 (2.6 g, 9.2 mmol) in 10 mLof methanol was added dropwise HCl/EtOH (4M, 30 mL) at rt. After 4 hoursof stirring at rt, the reaction mixture was concentrated, and remainingresidue was redissolved in a mixture of 10 mL of MeOH and 50 mL ofCH₂Cl₂, followed by the addition of 4 g of K₂CO₃. The resulting mixturewas filtered through a pad of Celite after 16 hours of stirring. Thefiltrate was concentrate under reduced pressure to give crudeBoc-protected Intermediate 15-4 as pale brown solid (1.1 g, 65%).

Example 16. Synthesis of Intermediate 16-2 Useful in Preparing CompoundsDescribed Herein Such as Compound 277

Titanium(IV) isopropoxide (10.2 g, 35.8 mmol) was added dropwise to asolution of 1-Boc-piperazine (4 g, 21.5 mmol) in 40 mL of MeOH. It wasthen followed by the addition of 1-ethylpiperidin-4-one (2.3 g, 17.9mmol) at rt. The reaction mixture was stirred at rt for 5 hours,followed by addition of sodium borohydride (0.68 g, 17.9 mmol). Theresulting mixture was quenched by water (4 mL) after additional 2 hoursof stirring. Inorganic precipitate was filtered and washed with ethylacetate. The combined organic phases were concentrated under reducedpressure and the residue was purified by column chromatography on silicagel (petroleum ether/ethyl acetate=1:1) to give Boc-protectedIntermediate 16-1 as pale yellow oil (3.1 g, 58%).

A solution of Boc-protected Intermediate 16-1 (3.1 g, 10.4 mmol) in 20mL of methanol was added dropwise to HCl/EtOH (4M, 30 mL) at rt. After 4hrs of stirring at rt, the reaction was concentrated and remainingresidue was redissolved in a mixture of 10 mL of MeOH and 50 mL ofCH₂Cl₂, followed by the addition of 4 g of K₂CO₃. The resulting mixturewas filtered through a pad of Celite after 16 hours of stirring. Thefiltrate was concentrate under reduced pressure to give Intermediate16-2 as yellow solid (2 g, 100%).

Example 17. Synthesis of Intermediate 17-2 Useful in Preparing CompoundsDescribed Herein Such as Compound 279

Titanium(IV) isopropoxide (10.2 g, 35.8 mmol) was added dropwise to asolution of 1-Boc-piperazine (4 g, 21.5 mmol) in 40 mL of MeOH. It wasthen followed by the addition of aldehyde (CAS #: 244-757-7) (3.6 g,17.9 mmol) at rt. The reaction mixture was stirred at rt for 5 hours,followed by addition of sodium borohydride (0.68 g, 17.9 mmol). Afteradditional 2 hours of stirring, the resulting mixture was quenched bywater (4 mL). Inorganic precipitate was filtered and washed with ethylacetate. The combined organic phases were concentrated under reducedpressure and the residue was purified by column chromatography on silicagel (petroleum ether/ethyl acetate=1:1) to give Boc-protectedIntermediate 17-1 as pale yellow waxy solid (5.6 g, 67%).

A solution of Boc-protected Intermediate 17-1 (5.6 g, 15 mmol) in 80 mLof methanol was added dropwise to HCl/EtOH (4M, 120 mL) at rt whilestirring. After 4 hours, the reaction was concentrated and remainingresidue was redissolved in a mixture of 20 mL of MeOH and 100 mL ofCH₂Cl₂, followed by the addition of 8 g of K₂CO₃. The resulting mixturewas filtered through a pad of Celite after 16 hours of stirring. Thefiltrate was concentrate under reduced pressure to give Intermediate17-2 as brown oil (4.1 g, 100%).

Example 18. Synthesis of Intermediates 18-13, 18-14 and 18-15 Useful inPreparing Compounds Described Herein

A solution of EtONa was prepared by dissolving Na (2.3 g) in absoluteEtOH (250 ml). Starting material 18-1 (14 g, 0.1 mol) was added dropwise to the solution of EtONa (0.1 mol). After stirring the at rt for 1hour Starting material 18-2 (12.2 g, 0.1 mol) was added in one portionand the reaction mixture was brought to reflux and stirred under refluxfor 3 hours. After cooling to rt, the reaction mixture was concentratedin vacuo and the residue was triturated with water (250 ml) followed byextraction with diethyl ether (4×125 mL). Combined organic layer waswashed water (2×150 mL), brine (2×150 mL) and dried over Na₂SO₄,filtered and evaporated in vacuo to give Intermediate 18-3 which wasused without further purification (22 g, 95%).

A solution of oxone (95 g, 0.625 mol) in water (400 mL) was addeddrop-wise at rt to a solution of Intermediate 18-3 (22 g, 0.097 mol) ina mixture of MeOH (200 ml) and THF (200 ml). After stirring at rt for 24hours, the reaction mixture was filtered and the filtrate was evaporatedin vacuo. The residue was extracted with DCM (2×200 mL). The combinedorganic layers were washed with water (3×100 mL), brine (3×100 mL),dried over Na₂SO₄, filtered and evaporated in vacuo. The product wasdried in vacuo and was used without additional purification (22.3 g,89%).

A solution of 18-4 (43 g, 0.167 mol), 18-5 (61 g, 0.51 mol) and HCOOH (2mL) in toluene (150 mL) was stirred under reflux for 8 hours. Thereaction mixture was cooled down to rt, the precipitate formed wasfiltered off and washed with toluene (2×50 mL) and dried in vacuo (42.3g, 81%).

A solution of 18-6 (21.3 g, 67.9 mmol) and 18-7 (11.7 g, 67.9 mmol) inp-xylene (75 mL) was stirred under reflux for 48 hours. The reactionmixture was cooled down to rt. The precipitate was filtered off, washedwith p-xylene and recrystallized from benzene (17.3 g, 58%).

Trimethylsilyl polyphosphate (PPSE, 230 g) was added to a solution of18-8 (22.85 g, 52 mmol) in o-xylene (230 ml) and the reaction mixturewas stirred under reflux for 120 hours. The reaction was thenconcentrated under vacuo and the residue was triturated with water (250mL). The precipitate was filtered off and was triturated with boilingi-PrOH (250 mL). The precipitate was filtered off and dried in vacuo(8.8 g, 43%).

A solution of 18-9 (8.8 g, 22.3 mmol), Et₃N (5.6 g, 55.8 mmol), Xantphos(1.03 g, 1.8 mmol), Pd(OAc)₂ (0.3 g, 1.3 mol) in MeOH (150 mL) was keptin a pressure reactor for 18 hours at 120° C. and 10 atm of CO. Thereaction mixture was cooled down, the precipitate was filtered off andwashed with MeOH (50 mL). The filtrate was evaporated in vacuo, and theresidue was vacuum dried (7.6 g, 91%).

Ester 18-10 (7.6 g, 20 mmol) was dissolved upon heating in i-PrOH (25mL). To this solution was added KOH (3.41 g, 60 mmol) in i-PrOH (75 mL).After stirring for 45 minutes, the reaction mixture was cooled down tort and concentrated under vacuo. The residue was stirred with charcoalsuspended in water (50 mL) for 15 minutes. The charcoal was filtered offand the filtrate was acidified with concentrated HCl to pH=1. Theprecipitate was filtered off and dried in vacuo (7.0 g, 98%).

Oxalyl chloride (39.4 mL, 0.46 mol) was carefully added in one portionto a suspension of 18-11 (6.6 g, 18.4 mmol) in anhydrous CHCl₃ (250 mL).The reaction mixture was stirred under reflux until all stating materialwas dissolved (6 hours). The reaction mixture was cooled down andevaporated and dried in vacuo. Acid chloride 18-12 was further usedwithout additional purification.

A solution of amine (15.25 mmol) in anhydrous toluene (20 mL) was addedslowly drop wise to a solution of 18-12 (2.4 g, 6.1 mmol) in anhydrousCH₂Cl₂ (100 mL) while maintaining reaction temperature at −20° C.). Itwas then followed by addition of N,N-diethylethylenediamine (0.78 g,6.71 mmol) and Et₃N (1.23 g, 12.2 mmol) in 10 mL of toluene. Thereaction mixture was stirred for 15 minutes at −20° C., the reaction wasstopped by adding water (100 mL). The organic layer was washed withwater (2×100 mL), brine (100 mL), dried over Na₂SO₄ filtered andevaporated/dried in vacuo.

Intermediate 18-13 was recrystallized from toluene (3.46 g, 58%).

Intermediate 18-14 was purified by preparative column chromatography(CH₂Cl₂, MeOH (2.5%) followed by CH₂Cl₂ acetone (gradient 8-15%))(Yield: 2.65 g, 43%).

Intermediate 18-15 was purified by preparative column chromatographyCH₂Cl₂ MeOH (gradient 3-6%) (2.2 g, 30%).

Example 19. Synthesis of Intermediate 19-4 Useful in Preparing CompoundsDescribed Herein

A mixture of Et₃N (2.5 g, 25 mmol) and 19-2 (3.3 g, 20 mmol) was addeddrop-wise to a solution of 19-1 (2.52 g, 20 mmol) in CHCl₃ (50 mL) at25° C. The reaction mixture was stirred at 25° C. for 2 hours and waswashed with water (2×50 mL), organic layer was separated, dried overNa₂SO₄, filtered and evaporated/dried in vacuo (4.0 g, 95%). The productwas used without additional purification.

A solution of n-butyliodide (1.52 g, 8.3 mmol) in acetone (10 mL) wasadded drop-wise to a suspension of K₂CO₃ in a solution of 19-3 (1.6 g,7.5 mmol) in acetone (30 mL). The reaction mixture was stirred underreflux for 48 hours and after cooling down to room temperature thesolvent was removed in vacuo. The residue was triturated with water (50mL) and the product was extracted with CH₂Cl₂ (2×50 mL). The combinedorganic layer was separated, washed with water (2×50 mL), the organicphase was separated dried over Na₂SO₄, filtered and evaporated/dried invacuo to give Intermediate 19-4 (1.8 g, 92%).

Example 20. Synthesis of Chiral Sulfoxides

To a stirred solution of Sulfide 20-1 (600 mg, 1.03 mmol, 1. eq.) indichloromethane (18 mL, 30 volumes) was added (−)-Diisopropyl d-tartrate(484 mg, 2.07 mmol, 2.00 equiv) at around 20° C. This solution wasyellow in appearance after short mixing. Titanium isopropoxide (294 mg,1.03 mmol, 1.00 equiv) was then added dropwise. The reaction mixture wasthen cooled to 0° C. and cumeme hydroperoxide (197 mg, 1.03 mmol, 80%w/w solution, 1 equiv) added dropwise while maintaining the temperatureat 0° C. After stirring at 0° C. for 3 h, the reaction mixture wasquenched by adding 10 mL of 5% Na₂CO₃ and 5% Na₂SO₃ aqueous solution.The organic layer was separated and purified by flash chromatography toobtain Sulfoxide 20-2-R (500 mg, 81% yield, 88% ee).

To a stirred solution of Sulfide 20-1 (600 mg, 1.03 mmol, 1. eq.) indichloromethane (18 mL, 30 volumes) was added (+)-Diisopropyl d-tartrate(484 mg, 2.07 mmol, 2.00 equiv) at around 20° C. This solution wasyellow in appearance after short mixing. Titanium isopropoxide (294 mg,1.03 mmol, 1.00 equiv) was then added dropwise. The reaction mixture wasthen cooled to 0° C. and cumeme hydroperoxide (197 mg, 1.03 mmol, 80%w/w solution, 1 equiv) added dropwise while maintaining the temperatureat 0° C. After stirring at 0° C. for 3 h, the reaction mixture wasquenched by adding 10 mL of 5% Na₂CO₃ and 5% Na₂SO₃ aqueous solution.The organic layer was separated and purified by flash chromatography toobtain Sulfoxide 20-2-S (510 mg, 83% yield, 85% ee).

Example 21. Synthesis of Intermediate 21-1 and 21-2

To a stirred solution of 21-b (16.5 g, 88.6 mmol, 1.00 eq.) in 160 mL ofMeOH was added Titanium(IV) isopropoxide (50.5 g, 177.7 mmol, 2.00 eq.)at rt. It was then followed by the addition of 21-a (11.3 g, 88.8 mmol,1.00 eq.). The reaction mixture was stirred at 30° C. for 6 hrs,followed by addition of sodium borohydride (3.4 g, 89.6 mmol) aftercooling reaction mixture to 5° C. After additional 14 hrs of stirring atrt, the resulting mixture was quenched by water (20 mL). Inorganicprecipitate was filtered and washed with ethyl acetate. The combinedorganic phases were concentrated under reduced pressure and the residuewas diluted with 200 mL ethyl acetate. Inorganic precipitate wasfiltered again and the filtrate was washed with water 4×50 mL. Theaqueous phase was extracted with EtOAc 3×100 mL. The combined organicphases were concentrated under reduced pressure to give crude 21-c asyellow oil (˜24 g, crude). The yellow oil was dissolved in EtOAc (150mL) and H₂O (150 mL). The mixture was stirred and CH₃COOH was addeddropwise to adjust the pH of aqueous layer to 7. The aqueous layer wasseparated and the pH was adjusted to 9 by K₂CO₃. DCM (200 mL) was addedto extract Compound 1. The DCM layer was separated and concentrated toafford Compound 21-c as yellow oil (20.2 g, 76.5% yield).

A solution of Compound 21-c (20.2 g, 67.9 mmol) in 30 mL of EtOAc wasadded dropwise to HCl/EtOH (4M, 150 mL) at 30° C. After it was stirredat 30° C. for 12 hrs, the reaction mixture was filtered and the filtercake was washed by 20 mL of ethanol and 100 mL of EtOAc. The obtainedfilter cake was re-dissolved in a mixture of 25 mL of MeOH and 125 mL ofCH₂Cl₂, followed by the addition of K₂CO₃ (18 g, 130 mmol). Theresulting mixture was filtered through a pad of Celite after 2 hrs ofstirring. The filtrate was concentrated under reduced pressure to give21-1 as light-yellow oil (11 g, 82.1% yield).

To a solution of 21-1 (11 g, 55.7 mmol, 1.00 eq.) in 150 mL of MeOH wasadded 21-d (11.1 g, 55.7 mmol, 1.00 eq.) After the resulting reactionmixture was stirred at 60° C. for 5 hrs, it was cooled to 5° C.,followed by addition of sodium borohydride (2.1 g, 55.3 mmol, 1.00 eq.).After additional 12 hrs of stirring at rt, the resulting mixture wasquenched by water (16 mL). Inorganic precipitate was filtered and washedwith 100 mL of ethyl acetate. The combined organic phases wereconcentrated under reduced pressure and the residue was diluted with 150mL ethyl acetate. Inorganic precipitate was filtered again and thefiltrate was washed with water 4×50 mL. The aqueous phase was extractedwith EtOAc 3×100 mL. The combined organic phases were concentrated toabout in 150 mL total volume and additional 150 mL of H₂O was add to themixture. The mixture was stirred and CH₃COOH was added dropwise toadjust the pH of aqueous layer to 7. The aqueous layer was separated andthe pH was adjusted to 9 by K₂CO₃, followed by addition of 200 mL ofDCM. The DCM layer was separated and concentrated to afford 21-e aslight-yellow solid (10 g, 47.1% yield).

To a solution of 21-e (10 g, 26.3 mmol) in 20 mL of EtOAc was addeddropwise 70 mL of 4 M HCl/EtOH at 30° C. After it was stirred at 30° C.for 14 hrs, the reaction mixture was filtered and the filter cake waswashed by 20 mL ethanol and 30 mL EtOAc. The obtained white filter cakewas re-dissolved in a mixture of 25 mL of MeOH and 75 mL of CH₂Cl₂,followed by the addition of K₂CO₃ (10 g, 72.5 mmol). The resultingmixture was filtered through a pad of Celite after 2 hrs of stirring.The filtrate was concentrated under reduced pressure to give alight-yellow solid. The solid was dissolved in CH₃CN (8 mL), followed bysonication for 3 mins. The mixture was filtered and the filter-cake wasdried to afford 21-2 as a white solid (6.4 g, 86.8% yield).

Using the procedures described above, other amines corresponding to thesubstituent R¹ can be prepared by using suitable starting materials.

Compounds shown in Table 2 were or may be synthesized according to theprocedures described herein from starting materials or intermediatesdescribed herein or starting materials known in the art or can beprepared by methods known in the art. For example, Compounds 2-41 wereprepared according to procedures similar to those described in II-2A,I-1 to 1-5, I-6A; Compound 42 was prepared according to proceduressimilar to those described in II-2A, I-1 to 1-5, I-6A, 1-7; Compounds43, 44, 54, 68, 69, 71-74 and 113-115 were prepared according toprocedures similar to those described in II-B, I-1 to I-5, I-6A in theGeneral Synthesis.

TABLE 2 No MS (m/z) ¹H NMR 1 480 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24(t, 3H, J = 7.8 Hz), 2.37 (s, 3H), 2.42 (m, 4H), 2.73 (q, 2H, J = 9 Hz),3.29 (m, 4H), 5.25 (s, 2H), 7.34 (d, 2H, J = 8.4 Hz), 7.67 (dd, 1H, J =9, 1.8 Hz), 7.78 (d, 2H, J = 7.8 Hz), 8.10 (s, 1H), 8.22 (d, 1H, J = 9.6Hz), 9.41 (s, 1H) 2 465 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (t, 3H, J =7.8, 7.8 Hz), 1.61 (m, 4H), 1.67 (m, 2H), 2.73 (q, 2H, J = 9 Hz), 3.26(m, 4H), 5.26 (s, 2H), 7.35 (d, 2H, J = 8.4 Hz), 7.67 (dd, 1H, J = 9,2.4 Hz), 7.78 (d, 2H, J = 8.4 Hz), 8.04 (s, 1H), 8.16 (d, 1H, J = 9 Hz),9.28 (s, 1H) 3 467 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (t, 3H, J = 7.2,7.8 Hz), 2.73 (q, 2H, J = 9 Hz), 3.26 (m, 2H), 3.67 (m, 4H), 7.35 (d,2H, J = 8.4 Hz), 7.68 (dd, 1H, J = 9.6, 1.8 Hz), 7.80 (d, 2H, J = 8.4Hz), 8.04 (s, 1H), 8.26 (d, 1H, J = 7.8 Hz), 9.46 (s, 1H) 4 479 ¹HNMR(600 MHz, CDCl₃, 25° C.): 1.0 (d, 3H, J = 6.6 Hz), 1.22 (m, 1H), 1.24(t, 3H, J = 7.8, 7.8 Hz), 1.62 (m, 3H), 2.72 (q, 2H, J = 9 Hz), 3.17 (m,2H), 3.38 (m, 2H), 7.35 (d, 2H, J = 8.4 Hz), 7.64 (dd, 1H, J = 9, 2.4Hz), 7.77 (d, 2H, J = 8.4 Hz), 8.00 (s, 1H), 8.17 (d, 1H, J = 9.6 Hz),9.28 (s, 1H) 5 510 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.27 (t, 3H, J = 7.8,7.8 Hz), 2.69 (m, 4H), 2.75 (m, 4H), 3.42 (m, 4H), 3.75 (t, 2H, J = 4.8,4.8 Hz), 7.38 (d, 2H, J = 8.4 Hz), 7.69 (dd, 1H, J = 9, 1.8 Hz), 7.81(d, 2H, J = 8.4 Hz), 8.09 (d, 1H, J = 0.6 Hz), 8.35 (d, 1H, J = 9.6 Hz),9.31 (s, 1H) 6 494 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.13 (t, 3H, J = 7.2Hz), 1.24 (t, 3H, J = 7.8, 7.2 Hz), 2.45 (m, 4H), 2.51 (m, 2H), 2.72 (q,2H, J = 9 Hz), 3.32 (m, 4H), 7.35 (d, 2H, J = 8.4 Hz), 7.68 (dd, 1H, J =9, 1.8 Hz), 8.12 (d, 2H, J = 1.8 Hz), 8.23 (d, 1H, J = 9 Hz), 9.44 (s,1H) 7 494 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.23 (t, 3H, J = 7.2, 7.8 Hz),1.88 (m, 2H), 2.46 (s, 3H), 2.64 (m, 2H), 2.71 (m, 4H), 3.31 (m, 4H),7.36 (d, 2H, J = 8.4 Hz), 7.63 (dd, 1H, J = 9, 2.4 Hz), 7.82 (d, 2H, J =8.4 Hz), 8.19 (d, 1H, J = 3.6 Hz), 8.39 (s, 1H), 9.40 (s, 1H) 8 481¹HNMR (600 MHz, CDCl₃, 25° C.): 1.26 (t, 3H, J = 7.8 Hz), 1.63 (m, 2H),1.89 (m, 2H), 2.72 (q, 2H, J = 9.6 Hz), 3.27 (m, 2H), 3.39 (m, 2H), 7.37(d, 2H, J = 8.4 Hz), 7.68 (d, 1H, J = 2.4 Hz), 7.80 (d, 2H, J = 8.4 Hz),8.02 (s, 1H), 8.23 (d, 1H, J = 9 Hz), 9.32 (s, 1H) 9 538 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.26 (t, 3H, J = 7.8 Hz), 1.32 (t, 3H, J = 7.2 Hz), 2.72(q, 2H, J = 10.8, 9 Hz), 3.24 (m, 4H), 3.48 (m, 4H), 4.19 (q, 2HJ = 13.8Hz), 7.35 (d, 2H, J = 8.4 Hz), 7.71 (d, 1H, J = 1.8 Hz), 7.77 (d, 2H, J= 8.4 Hz), 7.95 (m, 1H, J = 0.6 Hz), 8.27 (d, 1H, J = 9 Hz), 9.43 (s,1H) 10 560 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (t, 3H, J = 7.8 Hz),2.73 (q, 2H, J = 9 Hz), 3.15 (m, 4H), 3.45 (m, 4H), 6.95 (m, 2H, J = 9Hz), 7.0 (m, 2H), 7.35 (d, 2H, J = 8.4 Hz), 7.70 (dd, 1H, J = 9, 1.8Hz), 7.80 (d, 2H, J = 8.4 Hz), 8.10 (s, 1H), 8.26 (d, 1H, J = 9 Hz),9.44 (s, 1H) 11 548 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.17 (t, 3H, J =7.8 Hz), 1.87 (m, 6H), 2.70 (q, 2H, J = 9 Hz), 2.89 (m, 4H), 3.35 (m,2H), 3.33 (m, 2H), 3.45 (m, 4H), 7.48 (d, 2H, J = 9 Hz), 7.83 (d, 2H, J= 8.4 Hz), 7.99 (d, 1H, J = 9 Hz), 8.18 (s, 1H), 8.35 (d, 1H, J = 9.6Hz), 9.44 (s, 1H) 12 557 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.20 (t, 3H, J= 7.8 Hz), 1.70 (m, 2H), 2.00 (m, 2H), 2.69 (q, 2H, J = 15, 15.6 Hz),2.94 (m, 2H), 3.89 (q, 2H, J = 11.4 Hz), 7.34 (m, 3H), 7.35 (m.2H), 7.45(d, 2H, J = 7.2 Hz), 7.69 (dd, 2H, J = 9, 1.8 Hz), 7.82 (d, 1H, 8.4 Hz),8.18 (s, 1H), 8.28 (d, 1H, J = 9 Hz), 9.49 (s, 1H) 13 542 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.25 (t, 3H, J = 7.8 Hz), 2.72 (q, 2H, J = 9.6 Hz),3.20 (m, 4H), 3.45 (m, 4H), 6.95 (m, 3H), 7.28 (m, 4H), 7.70 (d, 1H, J =8.4 Hz), 7.80 (d, 2H, J = 7.8 Hz), 8.11 (s, 1H), 8.26 (d, 1H, J = 9 Hz),9.47 (s, 1H) 14 451 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.23 (t, 3H, J = 7.8Hz), 2.04 (m, 4H), 2.71 (q, 2H, J = 9.6 Hz), 3.18 (m, 4H), 7.33 (d, 2H,J = 8.4 Hz), 7.64 (dd, 1H, J = 9, 2.4 Hz), 7.67 (m, 1H)7.80 (d, 2H, J =8.4 Hz), 8.22 (d, 1H, J = 9 Hz), 9.43 (s, 1H) 15 427 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.24 (t, 3H, J = 7.8, 7.2 Hz), 1.59 (m, 2H), 1.81 (m,2H), 2.70 (q, 2H, J = 9.6 Hz), 3.20 (m, 2H), 3.55 (m, 2H), 3.94 (s, 3H),7.34 (d, 2H, J = 8.4 Hz), 7.41 (m, 1H), 7.47 (dd, 1H, J = 9, 2.4 Hz),7.78 (d, 1H, J = 8.4 Hz), 8.10 (d, 1H, J = 9 Hz), 9.23 (s, 1H) 16 484¹HNMR (600 MHz, CDCl₃, 25° C.): 1.23 (t, 3H, J = 7.8 Hz), 1.28 (t, 3H, J= 6.6.7.2 Hz), 2.70 (q, 2H, J = 9 Hz), 3.21 (m, 6H), 3.44 (m.2H), 3.92(s, 3H), 4.16 (q, 2H, J = 7.8 Hz), 7.28 (d, 1H, J = 3 Hz), 7.33 (d, 2H,J = 8.4 Hz), 7.49 (dd, 1H, J = 9.6, 2.4 Hz), 7.75 (d, 2H, J = 8.4 Hz),8.14 (d, 1H, J = 8.4 Hz), 9.29 (s, 1H) 17 506 ¹HNMR (600 MHz, CDCl₃, 25°C.): 1.22 (t, 3H, J = 7.8 Hz), 2.69 (q, 2H, J = 15 Hz), 3.04 (m, 4H),3.37 (m, 4H), 3.90 (s, 3H), 6.88 (m, 2H), 7.00 (m, 2H), 7.31 (d, 2H, J =6.6 Hz), 7.41 (m, 1H), 7.48 (dd, 1H, J = 9, 3 Hz), 7.77 (d, 2H, J = 7.2Hz), 8.11 (d, 1H, J = 9 Hz), 9.32 (s, 1H) 18 425 ¹HNMR (600 MHz, CDCl₃,25° C.): 1.22 (t, 3H, J = 7.2, 7.8 Hz), 1.26 (m, 4H), 1.61 (m, 2H), 1.76(m, 2H), 1.95 (m, 2H)2.66 (q, 2H, J = 9.6 Hz), 3.87 (m, 4H), 7.10 (m,1H), 7.30 (d, 2H.J = 9 Hz)7.32 (d, 2H, J = 3 Hz), 7.35 (dd, 1H, J = 9,2.4 Hz), 7.81 (d, 2H, J = 8.4 Hz), 7.88 (d, 1H, J = 9 Hz), 8.93 (s, 1H)19 437 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.27 (t, 3H, J = 7.8, 7.2 Hz),2.59 (q, 2H, J = 9.6 Hz), 3.41 (s, 3H), 6.67 (m, 2H), 6.75 (d, 1H, J = 3Hz), 6.89 (m, 2H)7.16 (d, 2H, J = 8.4 Hz), 7.30 (dd, 1H, J = 9.6, 3 Hz),7.75 (d, 2H, J = 8.4 Hz), 7.92 (d, 1H, J = 9 Hz), 8.55 (s, 1H), 9.14 (s,1H) 20 426 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.25 (t, 3H, J = 9 Hz), 2.74(q, 2H.J = 9 Hz)2.79 (s, 3H), 2.92 (m, 4H), 3.27 (m, 2H), 4.10 (s, 3H),4.52 (m, 2H), 7.40 (d, 2H, J = 8.4 Hz)7.46 (d, 2H, J = 9 Hz), 7.48 (dd,1H, J = 9, 2.4 Hz), 7.92 (d, 2H, J = 10.8 Hz), 8.06 (d, 1H, J = 9 Hz),8.83 (s, 1H) 21 411 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J =7.8, 7.2 Hz), 1.52 (m, 4H), 1.60 (m, 2H), 2.69 (q, 2H, J = 15 Hz), 3.20(m, 4H), 3.94 (s, 3H), 7.31 (d, 2H, J = 8.4 Hz), 7.43 (m, 2H), 7.77 (d,1H, J = 8.4 Hz), 8.06 (d, 1H, J = 9 Hz), 9.19 (s, 1H) 22 413 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.2, 7.8 Hz), 2.69 (q, 2H, J = 15Hz), 3.19 (m, 4H), 3.60 (m, 4H), 3.94 (s, 3H), 7.33 (d, 2H, J = 8.4 Hz),7.38 (d, 1H, J = 2.4 Hz), 7.48 (dd, 1H, J = 9.6, 3 Hz), 7.78 (d, 2H, J =8.4 Hz), 8.13 (d, 1H, J = 9 Hz), 9.35 (s, 1H) 23 425 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.97 (d, 3H, J = 9 Hz), 1.13 (m, 2H), 1.22 (t, 3H, J =7.2, 7.8 Hz), 1.54 (m, 3H), 2.69 (q, 2H, J = 15.6 Hz), 3.06 (m, 2H),3.35 (t, 2H, J = 11.4 Hz), 7.31 (d, 2H, J = 8.4 Hz), 7.39 (d, 1H, J =2.4 Hz), 7.44 (dd, 1H, J = 9, 2.4 Hz), 7.76 (d, 2H, J = 8.4 Hz), 8.06(d, 1H, J = 9 Hz), 9.21 (s, 1H) 24 440 ¹HNMR (600 MHz, CDCl₃, 25° C.):1.14 (m, 2H), 1.23 (t, 3H, J = 7.8 Hz), 2.07 (m, 2H), 2.42 (m, 6H), 2.71(q, 2H, J = 15.6 Hz), 3.31 (m, 4H), 3.96 (s, 3H), 7.31 (d, 2H, J = 8.4Hz), 7.44 (d, 2H, J = 2.4 Hz), 7.45 (dd, 1H, J = 9, 2.4 Hz), 7.75 (d,2H, J = 8.4 Hz), 8.08 (d, 1H, J = 9 Hz), 9.28 (s, 1H) 25 397 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.20 (t, 3H, J = 7.8, 7.2 Hz), 2.0 (m, 4H), 2.68(q, 2H, J = 15 Hz), 3.0 (m, 4H), 3.87 (s, 3H), 6.99 (s, 1H), 7.29 (d,2H, J = 8.4 Hz), 7.43 (dd, 1H, J = 9, 2.4 Hz), 7.78 (d, 2H, J = 8.4 Hz),8.12 (d, 1H, J = 9 Hz), 9.42 (s, 1H) 26 488 ¹HNMR (600 MHz, CDCl₃, 25°C.): 1.22 (t, 3H, J = 7.2, 7.8 Hz), 2.69 (q, 2H, J = 15, 7.2 Hz), 3.14(m, 4H), 3.35 (m, 4H), 6.88 (m, 3H), 7.29 (m, 4H), 7.38 (m, 1H), 7.46(dd, 1H, J = 15, 2.4 Hz), 7.75 (d, 2H, .8 Hz), 8.10 (d, 1H, J = 15 Hz),9.36 (s, 1H) 27 494 ¹HNMR (600 MHz, D6-DMSO, 25° C.): 1.16 (t, 3H, J =7.8, 7.2 Hz), 1.39 (m, 8H), 2.41 (m, 4H), 2.67 (q, 2H, J = 15 Hz), 2.92(m, 2H), 3.27 (m, 6H), 3.94 (s, 3H), 7.38 (d, 1H, J = 1.8 Hz), 7.44 (d,2H, J = 8.4 Hz), 7.61 (dd, 2H, J = 15, 2.4 Hz), 7.74 (d, 2H, J = 7.8Hz), 8.16 (d, 1H, J = 9.6 Hz)), 923 (s, 1H) 28 503 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.08 (t, 3H, J = 7.2, 7.8 Hz), 1.41 (m, 2H), 1.56 (m,2H), 2.56 (m, 2H), 2.64 (q, 2H, J = 15 Hz), 3.82 (m, 2H), 3.94 (s, 1H),5.19 (s, 1H), 7.24 (m, 1H), 7.38 (m, 2H), 7.46 (m, 4H), 7.63 (m, 2H),7.85 (d, 2H, J = 7.8 Hz), 8.14 (d, 1H, J = 9.6 Hz), 9.30 (s, 1H) 29 440¹HNMR (600 MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.2, 7.8 Hz), 2.02 (m,2H), 3.14 (s, 3H), 2.70 (q, 2H, J = 15.6 Hz), 2.79 (m, 2H), 2.91 (m2H),3.31 (m, 4H), 3.93 (s, 3H), 7.35 (d, 2H, J = 8.4 Hz), 7.43 (dd, 1H, J =9, 3 Hz), 7.53 (s, 1H), 7.81 (d, 2H, J = 8.4 Hz), 8.02 (d, 1H, J = 9.6Hz), 9.01 (s, 1H) 30 454 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.09 (m, 6H),1.25 (t, 3H, J = 7.8, 7.2 Hz), 1.83 (m, 3H), 2.43 (m, 3H), 2.72 (q, 2H,J = 15 Hz), 3.23 (m, 3H), 4.00 (s, 3H), 7.32 (d, 2H, J = 7.8 Hz), 7.47(m, 2H), 7.74 (d, 2H, J = 8.4 Hz), 8.08 (d, 1H, J = 9.6 Hz), 9.28 (m,1H) 31 425 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.21 (t, 3H, J = 7.8 Hz),1.68 (m, 8H), 2.71 (q, 2H, J = 9.6 Hz), 3.26 (m, 4H), 3.93 (s, 3H), 7.32(d, 2H, J = 8.4 Hz), 7.40 (d, 1H, J = 2.4 Hz), 7.43 (dd, 1H, J = 9, 3Hz), 7.80 (d, 2H, J = 8.4 Hz), 8.05 (d, 1H, J = 9 Hz), 9.19 (s, 1H) 32410 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.21 (t, 3H, J = 7.8 Hz), 2.34 (m,8H), 2.53 (s, 3H), 2.69 (q, 2H, J = 15 Hz), 3.26 (s, 3H), 7.31 (d, 2H, J= 7.8 Hz), 7.63 (dd, 1H, J = 9, 1.8 Hz), 7.76 (d, 2H, J = 8.4 Hz), 8.0(s, 1H), 8.09 (d, 1H, J = 8.4 Hz), 9.43 (s, 1H) 33 424 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.8 Hz), 2.19 (m, 2H), 2.55 (s, 6H),2.69 (m, 2H), 2.84 (m, 2H), 3.03 (m, 2H), 3.30 (m.2H), 3.54 (m, 2H),7.36 (d, 2H, J = 8.4 Hz), 7.61 (dd, 1H, J = 9, 1.2 Hz), 7.80 (d, 2H, J =7.8 Hz), 7.87 (s, 1H), 8.03 (dd, 1H, J = 9 Hz), 9.00 (m, 1H) 34 411¹HNMR (600 MHz, CDCl₃, 25° C.): 1.21 (t, 3H, J = 7.8 Hz), 1.52 (m, 2H),1.78 (m, 2H), 2.55 (s, 3H), 2.69 (q, 2H, J = 9 Hz), 3.21 (m, 2H), 3.31(m, 2H), 3.91 (m, 1H), 7.31 (d, 2H, J = 8.4 Hz), 7.63 (dd, 1H, J = 8.4,1.2 Hz), 7.75 (d, 2H, J = 8.4 Hz), 7.90 (m, 1H), 8.08 (d, 1H, J = 9.6Hz), 9.33 (s, 1H) 35 478 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.16 (t, 3H,J = 7.2 Hz), 1.40 (m, 4H), 1.52 (m, 4H), 2.39 (m, 4H), 2.55 (s, 3H),2.67 (q, 2H, J = 14.4 Hz), 2.88 (m, 2H), 3.30 (m, 4H), 7.42 (d, 2H, J =7.8 Hz), 7.74 (d, 2H.J = 7.8 Hz), 7.78 (d, 1H, J = 9 Hz), 8.04 (m, 1H),8.08 (d, 1H, J = 3 Hz), 9.33 (s, 1H) 36 395 ¹HNMR (600 MHz, CDCl₃, 25°C.): 1.21 (t, 3H, J = 7.2 Hz), 1.50 (m, 4H), 1.61 (m, 2H), 2.69 (q, 2H,J = 15 Hz), 3.19 (m, 2H), 7.30 (d, 2H, J = 7.8 Hz), 7.61 (dd, 1H, J =8.4, 1.2 Hz), 7.76 (d, 2H, J = 8.4 Hz), 7.94 (m, 1H), 8.05 (d, 1H, J =8.4 Hz), 9.32 (s, 1H) 37 414 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (t,3H, J = 7.8 Hz), 2.35 (s, 3H), 2.39 (m, 4H), 2.70 (q, 2H, J = 15 Hz),3.25 (m, 4H), 7.30 (d, 2H, J = 7.8 Hz), 7.57 (m, 1H), 7.78 (d, 2H, J =8.4 Hz), 7.87 (dd, 1H, J = 9.6, 2.4 Hz), 8.18 (q, 1H, J = 9 Hz), 9.40(s, 1H) 38 428 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.23 (t, 3H, J = 7.2 Hz),1.97 (m, 2H), 2.48 (s, 3H), 2.70 (m, 4H), 2.82 (m, 2H), 3.30 (m, 2H),3.37 (m.2H), 7.35 (d, 2H, J = 7.8 Hz), 7.54 (m, 1H), 7.81 (d, 2H, J =8.4 Hz), 7.93 (d, 1H, J = 9 Hz), 8.14 (q, 1H, J = 9 Hz), 9.20 (m, 1H) 39415 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.8 Hz)1.56 (m,2H), 1.81 (m, 2H), 2.69 (q, 2H, J = 15 Hz), 3.19 (m, 2H), 3.32 (m, 2H),3.92 (m, 1H), 7.36 (d, 2H, J = 8.4 Hz), 7.56 (m, 1H), 7.76 (m, 3H), 8.11(m, 1H), 9.30 (s, 1H) 40 482 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.16 (t,3H, J = 7.2, 7.8 Hz), 1.40 (m, 8H), 2.39 (m, 5H), 2.68 (q, 2H, J = 15Hz), 2.90 (m, 2H), 3.32 (m, 4H), 7.44 (d, 2H, J = 7.8 Hz), 7.78 (d, 2H.J= 7.2 Hz), 7.78 (m, 1H), 8.02 (d, 1H, J = 8.4 Hz), 8.26 (m, 1H), 9.36(s, 1H) 41 399 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.23 (t, 3H, J = 7.8 Hz),1.58 (m, 4H), 1.65 (m, 2H), 2.70 (q, 2H, J = 15.6 Hz), 3.25 (m, 2H),7.33 (d, 2H, J = 8.4 Hz), 7.51 (m, 1H), 7.78 (m, 3H), 8.19 (m, 1H), 9.25(s, 1H) 42 538 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.16 (t, 3H, J = 7.8Hz), 1.66 (m, 2H), 2.67 (q, 2H, J = 9 Hz), 2.76 (m, 2H), 2.90 (m, 2H),3.03 (m, 2H), 3.24 (m, 2H), 3.34 (s, 2H), 7.47 (d, 2H, J = 8.4 Hz), 7.84(d, 2H, J = 8.4 Hz), 7.92 (dd, 1H, J = 9, 2.4 Hz), 8.277 (d, 1H, J = 9.6Hz), 8.53 (s, 1H), 9.39 (s, 1H) 43 550 ¹HNMR (600 MHz, D₆-DMSO, 25° C.):1.41 (m, 4H), 1.53 (m, 6H), 2.45 (m, 4H), 3.07 (m, 2H), 3.20 (m, 2H),3.32 (m, 1H), 3.84 (s, 3H), 7.12 (d, 2H, J = 9 Hz), 7.84 (d, 2H, J = 9Hz), 7.93 (d, 1H, J = 9 Hz), 8.15 (s, 1H), 8.28 (d, 1H, J = 7.8 Hz),9.35 (s, 1H) 44 483 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.43 (m, 2H), 1.61(m, 4H), 1.68 (m, 2H), 3.06 (m, 2H), 3.20 (m, 2H), 3.72 (m, 1H), 3.85(s, 3H), 4.77 (d, 1H, J = 4.2 Hz), 7.13 (d, 2H, J = 9 Hz), 7.85 (d, 2H,J = 9 Hz), 7.92 (dd, 1H, J = 9.6, 2.4 Hz)8.10 (s, 1H), 8.26 (d, 1H, J =9.6 Hz), 9.31 (s, 1H) 45 566 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (t,3H, J = 7.8 Hz), 2.72 (q, 2H, J = 15 Hz)), 3.35 (m, 4H), 3.37 (m, 4H),6.90 (d, 2H, J = 9 Hz), 7.35 (d, 2H, J = 7.8 Hz), 7.55 (d, 2H, J = 9Hz), 7.70 (dd, 1H, J = 9, 1.8 Hz), 7.78 (d, 2H, J = 8.4 Hz), 7.99 (s, 1Hz), 8.34 (d, 1H, J = 9.6 Hz), 9.28 (s, 1H) 46 534 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.66 (t, 3H, J = 7.8 Hz), 1.46 (m, 2H), 1.75 (m, 6H),2.51 (m, 2H), 2.68 (q, 2H, J = 15 Hz), 2.97 (m, 4H), 3.33 (m, 5H), 7.47(d, 2H, J = 7.8 Hz), 7.84 (d, 2H, J = 6.6 Hz), 7.86 (d, 1H, J = 9 Hz),8.16 (s, 1H), 8.32 (d, 1H, J = 9 Hz), 9.41 (s, 1H) 47 537 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.8 Hz), 1.29 (t, 3H, J = 7.2 Hz),1.70 (m, 2H), 1.87 (m, 2H), 2.50 (m, 1H), 2.70 (q, 2H, J = 15.6 Hz)),3.21 (m, 2H), 3.34 (m, 2H), 4.17 (q, 2H, J = 15 Hz), 7.34 (d, 2H, J =9.6 Hz), 7.64 (dd, 1H, J = 9, 1.8 Hz), 7.77 (d, 2H, J = 8.4 Hz), 7.95(s, 1 Hz), 8.21 (d, 1H, J = 9 Hz), 9.33 (s, 1H) 48 495 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.2 Hz), 1.28 (m, 2H), 1.71 (m, 3H),2.70 (q, 2H, J = 15 Hz), 3.19 (m, 2H), 3.97 (m, 2H), 3.57 (d, 2H, J = 6Hz), 7.33 (d, 2H, J = 8.4 Hz), 7.62 (dd, 1H, J = 9, 2.4 Hz), 7.77 (d,2H, J = 8.4 Hz), 7.96 (s, 1H), 8.18 (d, 1H, J = 9.6 Hz), 9.29 (s, 1H) 49501 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.21 (t, 3H, J = 7.8 Hz), 2.58 (s,3H), 2.68 (q, 2H, J = 15 Hz), 4.53 (s, 2H), 7.19 (m, 2H), 7.30 (m, 3H),7.33 (d, 2H, J = 7.8 Hz), 7.46 (s, 1H), 7.58 (dd, 1H, J = 9, 1.8 Hz),7.82 (d, 2H, J = 8.4 Hz), 8.16 (d, 1H, J = 9 Hz), 9.36 (s, 1H) 50 495¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.14 (t, 3H, J = 7.8 Hz), 2.13 (s,3H), 2.32 (m, 2H), 2.64 (m, 4H), 2.81 (m, 4H), 3.33 (s, 1H), 7.45 (d,2H, J = 7.8 Hz), 7.79 (m, 2H), 7.92 (m, 1H), 7.96 (m, 2H), 8.97 (s, 1H)51 449 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.20 (t, 3H, J = 7.8 Hz), 2.65(q, 2H, J = 15.6 Hz), 6.96 (m, 1H), 7.23 (d, 2H, J = 8.4 Hz), 7.41 (d,2H, J = 8.4 Hz), 7.75 (dd, 1H, J = 9, 1.8 Hz), 8.0 (s, 1H), 8.32 (d, 1H,J = 9 Hz), 8.65 (s, 1H), 9.78 (s, 1H) 52 523 ¹HNMR (600 MHz, D₆-DMSO,25° C.): 1.22 (t, 3H, J = 7.2 Hz), 1.67 (t, 3H, J = 5.4 Hz), 2.69 (q,2H, J = 16.8 Hz), 3.33 (m, 4H), 4.01 (m, 4H), 7.34 (d, 2H, J = 7.8 Hz),7.66 (dd, 1H, J = 9, 1.8 Hz), 7.77 (d, 2H, 7.8 Hz), 8.01 (m, 1H), 8.27(d, 1H, J = 9 Hz), 9.43 (s, 1H) 53 509 ¹HNMR (600 MHz, D₆-DMSO, 25° C.):1.16 (t, 3H, J = 7.2 Hz), 1.37 (m, 2H), 1.66 (m, 2H), 2.67 (q, 2H, J =15 Hz), 3.0 (m, 2H), 3.24 (m, 2H), 7.43 (d, 2H, J = 8.4 Hz), 7.78 (d,2H, J = 8.4 Hz), 7.95 (dd, 1H, J = 9, 1.2 Hz), 8.13 (m, 1H), 8.30 (d,1H, J = 9 Hz), 9.38 (s, 1H), 12.22 (s, 1H) 54 545 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.15 (m, 2H), 1.23 (m, 3H), 1.41 (m, 8H), 2.39 (m,2H), 2.99 (m, 2H), 3.19 (m, 2H), 8.0 (d, 1H, J = 9 Hz), 8.11 (m, 4H),8.20 (s, 1H), 8.35 (d, 1H, J = 9 Hz), 9.45 (s, 1H) 55 503 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 1.17 (t, 3H, J = 7.2 Hz), 1.39 (m, 6H), 1.88 (m,4H), 2.41 (m, 4H), 2.68 (q, 2H, J = 15 Hz), 2.93 (m, 3H), 3.34 (m, 3H),4.34 (s, 1H), 7.45 (m, 2H), 7.78 (m, 2H), 7.91 (m, 1H), 8.21 (m, 2H),9.36 (s, 1H) 56 580 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.41 (m, 4H), 1.53(m, 6H), 2.43 (m, 4H), 3.07 (m, 2H), 3.20 (m, 5H), 3.79 (s, 3H), 3.84(s, 3H), 7.17 (m, 1H), 7.32 (m, 1H), 7.47 (m, 1H), 7.95 (d, 1H, J = 7.2Hz), 8.15 (s, 1H), 8.29 (d, 1H, J = 3 Hz), 9.34 (s, 1H) 57 526 ¹HNMR(600 MHz, CDCl₃, 25° C.): 1.95 (m, 2H), 2.46 (s, 3H), 2.72 (m, 4H), 3.38(m, 4H), 3.91 (s, 3H), 3.93 (s, 3H), 6.95 (d, 1H, J = 9 Hz), 7.38 (d,2H, J = 1.2 Hz), 7.51 (d, 1H, J = 8.4 Hz), 7.61 (d, 1H, J = 7.8 Hz),8.15 (d, 1H, J = 9 Hz), 8.36 (s, 1H), 9.24 (s, 1H) 58 513 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 1.43 (m, 2H), 1.69 (m, 2H), 1.68 (m, 2H), 3.16(m, 2H), 3.21 (m, 2H), 3.73 (m, 1H), 3.82 (s, 3H), 3.84 (s, 3H), 4.79(d, 1H, J = 3 Hz), 7.15 (d, 1H, J = 9 Hz), 7.38 (d, 1H, J = 1.2 Hz),7.46 (dd, 1H, J = 8.4, .2 Hz), 7.92 (dd, 1H, J = 9, 1.2 Hz), 8.10 (s,1H), 8.26 (d, 1H, J = 9.6 Hz), 9.30 (s, 1H) 59 565 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.18 (m, 4H), 1.47 (m, 2H), 1.72 (m, 6H), 2.74 (m,3H), 2.97 (m, 2H), 3.45 (m, 2H), 8.01 (d, 1H, J = 9.6 Hz), 8.20 (m, 3H),8.37 (d, 1H, J = 9.6 Hz), 8.41 (d, 2H, J = 9 Hz), 9.49 (s, 1H) 60 511¹HNMR (600 MHz, CDCl₃, 25° C.): 1.85 (m, 2H), 2.43 (s, 3H), 2.62 (m,2H), 2.68 (m, 2H), 3.19 (m, 2H), 3.27 (m, 2H), 7.67 (dd, 1H, J = 9.6,2.4 Hz), 8.09 (d, 2H, J = 3.6 Hz), 8.23 (d, 1H, J = 9 Hz), 8.37 (m, 3H),9.45 (s, 1H) 61 498 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.18 (m, 2H), 1.52(m, 2H), 3.04 (m, 2H), 3.15 (m, 2H), 3.61 (m, 1H), 4.71 (d, 1H, J = 4.2Hz), 7.99 (dd, 1H, J = 9.6, 1.8 Hz), 8.14 (s, 1H), 8.17 (d, 2H, J = 9Hz), 8.34 (d, 1H, J = 9 Hz), 8.39 (d, 2H, J = 3 Hz), 9.44 (s, 1H) 62 4691HNMR (600 MHz, D₆-DMSO, 25° C.): 1.17 (t, 3H, J = 7.2 Hz), 1.36 (t, 3H,J = 6.6 Hz), 1.45 (m, 2H), 1.69 (m, 2H), 2.69 (q, 2H, J = 15 Hz), 3.09(m, 2H), 3.71 (m, 1H), 4.73 (q, 2H, J = 14.4 Hz), 4.80 (d, 1H, J = 3.6Hz), 7.46 (d, 2H, J = 8.4 Hz), 7.83 (d, 2H, J = 7.8 Hz), 8.18 (d, 1H, J= 8.4 Hz), 8.31 (d, 1H, J = 8.4 Hz), 8.90 (s, 1H), 9.34 (s, 1H) 63 482¹HNMR (600 MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.8 Hz), 1.43 (t, 3H, J= 7.2 Hz), 1.99 (m, 2H), 2.47 (s, 3H), 2.70 (m, 4H), 2.85 (m, 2H), 3.32(m, 2H), 3.51 (m, 2H), 4.43 (q, 2H, J = 14.4 Hz), 7.56 (d, 2H, J = 8.4Hz), 7.82 (d, 2H, J = 7.8 Hz), 8.16 (d, 1H, J = 8.4 Hz), 8.35 (dd, 1H, J= 8.4, 1.2 Hz), 9.00 (s, 1H), 9.36 (s, 1H) 64 536 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.17 (t, 3H, J = 7.8 Hz), 1.37 (t, 3H, J = 7.2 Hz),1.46 (m, 8H), 1.87 (m, 2H), 2.46 (m, 2H), 2.69 (q, 2H, J = 15 Hz), 3.18(m, 4H), 3.35 (m, 3H), 4.38 (q, 2H, J = 13.8 Hz), 7.47 (d, 2H, J = 7.2Hz), 7.83 (m, 2H), 8.21 (m, 1H), 8.33 (m, 1H), 9.36 (m, 1H), 9.77 (m,1H) 65 441 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.17 (t, 3H, J = 7.2 Hz),1.37 (t, 3H, J = 6.6 Hz), 1.62 (m, 2H), 2.66 (q, 2H, J = 31 Hz), 3.09(m, 2H), 3.24 (m, 3H), 3.66 (m, 1H), 4.80 (d, 1H, J = 3.6 Hz), 7.45 (d,2H, J = 8.4 Hz), 7.80 (d, 2H, J = 8.4 Hz), 8.14 (d, 1H, J = 8.4 Hz),8.34 (dd, 1H, J = 9, 1.2 Hz), 8.85 (d, 1H, J = 1.2 Hz), 9.34 (s, 1H) 66454 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.17 (t, 3H, J = 7.8 Hz), 2.07 (m,2H), 2.64 (s, 3H), 2.70 (q, 2H, J = 15 Hz), 3.13 (m, 8H), 7.15 (d, 2H, J= 8.4 Hz), 7.87 (d, 2H, J = 8.4 Hz), 8.18 (d, 1H, J = 8.4 Hz), 8.38 (dd,1H, J = 9, 1.2 Hz), 8.75 (s, 1H), 9.36 (s, 1H) 67 508 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.15 (t, 3H, J = 7.2 Hz), 1.26 (m, 2H), 1.50 (m, 2H),1.75 (m, 6H), 2.66 (q, 2H, J = 15 Hz), 2.83 (m, 4H), 3.02 (m, 3H), 3.82(m, 2H), 7.45 (d, 2H, J = 7.2 Hz), 7.79 (d, 2H, J = 8.4 Hz), 8.16 (d,1H, J = 9 Hz), 8.36 (d, 1H, J = 9 Hz), 8.77 (m, 1H), 9.40 (m, 1H) 68 4851HNMR (400 MHz, CDCl3, 25° C.): 0.95 (t, 6H, J = 6.8 Hz), 3.53 (q, 4H, J= 13.6 Hz), 3.91 (s, 3H), 3.94 (s, 3H), 6.95 (d, 1H, J = 9.2 Hz), 7.38(d, 1H, J = 2.4 Hz), 7.53 (dd, 1H, J = 8.4, 2 Hz), 7.63 (dd, 1H, J =8.8, 2 Hz), 7.88 (d, 1H, J = 0.8 Hz), 8.29 (d, 1H, J = 8.4 Hz), 9.26 (s,1H) 69 487 ¹HNMR (400 MHz, D₆-DMSO, 25° C.): 1.74 (m, 2H), 3.50 (q, 2H,J = 10.8 Hz), 3.82 (m, 8H), 4.79 (t, 1H, J = 4.4 Hz), 7.15 (d, 1H, J =8.4 Hz), 7.57 (t, 1H, J = 5.2 Hz), 7.62 (dd, 1H, J = 8.4, 2.4 Hz), 7.77(dd, 1H, J = 9.2, 1.6 Hz), , 7.96 (d, 1H, J = 5.2 Hz), 8.19 (d, 1H, J =2 Hz), 8.95 (s, 1H) 70 513 ¹HNMR (400 MHz, CDCl₃, 25° C.): 1.55 (m, 1H),1.85 (m, 2H), 2.05 (m, 1H), 3.20 (m, 1H), 3.33 (m, 2H), 3.62 (m, 1H),3.91 (s, 3H), 3.96 (s, 3H), 4.01 (m, 1H), 6.98 (d, 1H, J = 8.4 Hz), 7.42(d, 1H, J = 2 Hz), 7.53 (dd, 1H, J = 8.8, 2.4 Hz), 7.64 (dd, 1H, J =9.2, 2 Hz), 8.06 (s, 1H), 8.19 (d, 1H, J = 10 Hz), 8.96 (s, 1H) 71 513¹HNMR (400 MHz, CDCl₃, 25° C.): 0.73 (t, 6H, J = 8.8 Hz), 1.37 (m, 4H),3.37 (m, 4H), 3.91 (s, 3H), 3.93 (s, 3H), 6.94 (d, 1H, J = 8.4 Hz), 7.38(d, 1H, J = 2 Hz), 7.52 (dd, 1H, J = 8.4, 2 Hz), 7.59 (dd, 1H, J = 10,3.2 Hz), 7.93 (d, 1H, J = 1.2 Hz), 8.13 (d, 1H, J = 8.8 Hz), 9.20 (s,1H) 72 517 ¹HNMR (400 MHz, D₆-DMSO, 25° C.): 3.33 (m, 10H), 3.82 (d,6H), 7.13 (d, 2H, J = 9 Hz), 7.11 (d, 1H, J = 8.4 Hz), 7.53 (d, 1H, J =2 Hz), 7.62 (dd, 1H, J = 10.4, 2.4 Hz), 7.75 (dd, 1H, J = 8.4, 1.6 Hz),7.82 (d, 1H, J = 8.8 Hz), 7.91 (d, 1H, J = 1.2 Hz), 8.79 (s, 1H) 73 473¹HNMR (400 MHz, D₆-DMSO, 25° C.): 3.60 (q, 2H, J = 10 Hz), 3.82 (m, 8H),5.33 (t, 1H, J = 4.8 Hz), 7.14 (d, 1H, J = 8.4 Hz), 7.52 (d, 1H, J = 6Hz), 7.65 (dd, 1H, J = 8.4, 2.4 Hz), 7.77 (dd, 1H, J = 9.2, 1.6 Hz),7.82 (t, 1H, J = 4.8 Hz), 7.95 (d, 1H, J = 8.8 Hz), 8.23 (d, 1H, J = 2.4Hz), 8.95 (s, 1H) 74 541 ¹HNMR (400 MHz, CDCl₃, 25° C.): 0.77 (t, 6H, J= 11.2 Hz), 1.12 (m, 4H), 1.32 (m, 4H), 3.44 (m, 4H), 3.92 (s, 3H), 3.93(s, 3H), 6.95 (d, 1H, J = 8.4 Hz), 7.37 (d, 1H, J = 2.4 Hz), 7.51 (dd,1H, J = 8.8, 2.4 Hz), 7.61 (dd, 1H, J = 8.8, 2 Hz), 7.91 (d, 1H, J = 1.2Hz), 8.25 (s, 1H), 9.24 (s, 1H) 75 442 ¹HNMR (400 MHz, CDCl₃, 25° C.):1.25 (t, 3H, J = 11.4 Hz), 1.78 (m, 2H), 2.04 (m, 2H), 2.41 (m, 4H),2.72 (q, 2H, J = 15.2 Hz), 3.47 (m, 2H), 3.63 (m, 2H), 4.08 (m, 1H),7.39 (d, 2H, J = 5.6 Hz), 7.80 (d, 2H, J = 12.6 Hz), 8.37 (d, 1H, J =8.8 Hz), 8.53 (dd, 1H, J = 9.2, 2.4 Hz), 9.15 (d, 1H, J = 2.4 Hz), 9.21(s, 1H) 76 455 ¹HNMR (400 MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.6 Hz),1.94 (m, 2H), 2.54 (s, 3H), 2.70 (m, 4H), 2.85 (m, 2H), 3.40 (m, 2H),3.48 (m, 2H), 7.37 (d, 2H, J = 8 Hz), 7.82 (d, 2H, J = 8.4 Hz), 8.22 (d,1H, J = 9.2 Hz), 8.49 (dd, 1H, J = 8.4, 2.4 Hz), 9.37 (s, 1H), 9.65 (s,1H) 77 509 ¹HNMR (400 MHz, D₆-DMSO, 25° C.): 1.17 (t, 3H, J = 7.6 Hz),1.44 (m, 4H), 1.57 (m, 6H), 2.41 (m, 4H), 2.68 (q, 2H, J = 15.2 Hz),3.28 (m, 5H), 7.47 (d, 2H, J = 8.4 Hz), 7.84 (d, 2H, J = 8 Hz), 8.30 (d,1H, J = 9.2 Hz), 8.58 (dd, 1H, J = 9.2, 2.4 Hz), 9.10 (d, 1H, J = 1.2Hz), 9.42 (s, 1H) 78 414 ¹HNMR (400 MHz, CDCl₃, 25° C.):, 0.93 (t, 6H, J= 6.4 Hz), 1.22 (t, 3H, J = 7.6 Hz), 2.70 (q, 2H, J = 15.2 Hz), 3.59 (q,2H, J = 14.4 Hz), 7.35 (d, 2H, J = 8.4 Hz), 7.82 (d, 2H, J = 8 Hz), 8.27(d, 1H, J = 9.2 Hz), 8.49 (dd, 1H, J = 9.2, 2.4 Hz), 8.99 (d, 1H, J =2.4 Hz), 9.40 (s, 1H) 79 395 1HNMR (600 MHz, CDCl₃, 25° C.): 1.20 (t,3H, J = 7.8 Hz), 2.65 (q, 2H, J = 15 Hz), 3.71 (s, 3H), 6.28 (d, 1H, J =2.4 Hz), 7.23 (d, 2H, J = 15 Hz), 7.42 (d, 2H, J = 8.4 Hz), 7.54 (dd,1H, J = 9, 2.4 Hz), 8.07 (s, 1H), 8.18 (d, 1H, J = 9 Hz), 8.59 (s, 1H),9.59 (s, 1H) 80 437 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.20 (t, 3H, J = 7.2Hz), 1.33 (t, 3H, J = 7.2 Hz), 2.65 (q, 2H, J = 9.6 Hz), 4.34 (q, 2H, HJ= 20.4 Hz), 7.24 (d, 2H, J = 8.4 Hz), 7.43 (d, 2H, J = 8.4 Hz), 7.90 (d,1H, J = 1.8 Hz), 8.10 (s, 1H), 8.31 (d, 1H, J = 9 Hz), 8.37 (dd, 1H, J =9, 1.8 Hz), 8.65 (s, 1H), 9.83 (s, 1H) 81 453 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.79 (t, 6H, J = 7.2 Hz), 1.21 (t, 3H, J = 7.8 Hz), 2.69 (q, 2H, J= 14.4 Hz), 3.42 (q, 4H, J = 14.4 Hz), 7.33 (d, 2H, J = 8.4 Hz), 7.60(dd, 1H, J = 9.6, 2.4 Hz), 7.82 (d, 2H, J = 8.4 Hz), 7.86 (d, 1H, J =0.6 Hz)), 8.18 (d, 1H, J = 9 Hz), 9.41 (s, 1H) 82 481 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.26 (t, 3H, J = 7.8 Hz), 1.50 (m, 1H), 1.81 (m, 2H),1.96 (m, 1H), 2.74 (q, 2H, J = 15.6 Hz), 3.12 (m, 1H), 3.27 (m, 1H),3.36 (m, 1H), 3.58 (dd, J = 11.4, 1.8 Hz), 3.95 (m, 1H), 7.38 (d, 2H, J= 8.4 Hz), 7.66 (dd, 1H, J = 9.6, 2.4 Hz), 7.82 (d, 2H, 8.4 Hz), 8.09(m, 1H), 8.27 (d, 1H, J = 9 Hz), 9.13 (s, 1H) 83 442 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.17 (t, 3H, J = 7.8 Hz), 2.18 (s, 3H), 2.69 (m, 2H),3.10 (m, 4H), 3.31 (s, 1H), 3.92 (s, 3H), 7.45 (d, 2H, J = 8.4 Hz), 7.77(m, 2H), 7.91 (m, 1H), 7.95 (m, 1H), 8.09 (d, 1H, J = 9 Hz), 9.21 (s,1H) 84 483 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.14 (t, 3H, J = 7.8 Hz),1.38 (t, 3H, J = 7.2 Hz), 2.17 (m, 5H), 2.65 (m, 4H), 2.86 (m, 4H), 4.36(q, 2H, J = 13.2 Hz), 7.36 (m, 1H), 7.46 (m, 2H), 7.82 (m, 1H), 7.89 (m,1H), 7.93 (m, 1H), 8.21 (d, 1H, J = 9 Hz), 8.99 (s, 1H) 85 497 ¹HNMR(600 MHz, D₆-DMSO, 25° C.): 2.18 (s, 3H), 2.34 (m, 2H), 2.86 (m, 4H),3.30 (m, 2H), 3.91 (s, 1H), 7.13 (d, 2H, J = 7.8 Hz), 7.78 (dd, 1H, J =9, 2.4 Hz), 7.85 (d, 1H, J = 9 Hz), 7.96 (m, 2H), 8.26 (d, 1H, J = 9.6Hz), 8.31 (m, 1H), 8.96 (s, 1H) 86 451 1HNMR (600 MHz, CDCl₃, 25° C.):3.83 (s, 3H), 6.87 (d, 2H, J = 9 Hz), 6.97 (d, 1H, J = 0.6 Hz), 7.43 (d,2H, J = 8.4 Hz), 7.75 (d, 1H, J = 9, 2.4 Hz), 8.14 (s, 1H), 8.32 (d, 1H,J = 9.6 Hz), 8.66 (s, 1H) 87 509 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.74(t, 6H, J = 7.2 Hz), 1.08 (m, 4H), 1.23 (m, 7H), 2.69 (q, 2H, J = 15.6Hz), 3.35 (m, 4H), 7.33 (d, 2H, J = 7.8 Hz), 7.60 (dd, 1H, J = 9, 2.4Hz), 7.81 (d, 2H, J = 7.8 Hz), 7.89 (m, 1H), 8.17 (d, 1H, J = 9 Hz),9.36 (s, 1H) 88 527 ¹HNMR (400 MHz, D₆-DMSO, 25° C.): 2.18 (m, 5H), 234(m, 2H), 2.89 (m, 4H), 3.31 (s, 1H), 3.82 (s, 3H), 3.84 (s, 3H), 7.15(d, 1H, J = 9 Hz), 7.48 (m, 1H), 7.62 (m, 1H), 7.78 (dd, 1H, J = 9, 2.4Hz), 7.95 (d, 1H, J = 9 Hz), 8.40 (s, 1H), 8.97 (s, 1H) 89 481 ¹HNMR(400 MHz, CDCl₃, 25° C.): 3.86 (s, 3H), 3.90 (s, 3H), 6.83 (d, 1H, J =8.4 Hz), 6.94 (dd, 2H, J = 11.4, 1.8 Hz), 7.15 (dd, 1H, J = 14.4, 2.4Hz), 7.57 (dd, 1H, J = 9, 1.8 Hz), 8.14 (s, 1H), 8.32 (d, 1H, J = 9 Hz),8.68 (s, 1H), 9.76 (s, 1H) 90 535 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 2.01(m, 5H), 2.61 (m, 2H), 2.78 (m, 4H), 7.42 (m, 1H), 7.84 (m, 1H), 7.96(m, 4H), 8.12 (m, 2H), 9.00 (s, 1H) 91 489 ¹HNMR (600 MHz, CDCl₃, 25°C.): 6.95 (d, 1H, J = 1.8 Hz), 7.65 (q, 4H, J = 24 Hz), 7.79 (dd, 1H, J= 9, 2.4 Hz), 8.08 (s, 1H), 8.36 (d, 1H, J = 9 Hz), 8.66 (s, qH), 9.80(s, 1H) 92 539 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.89 (t, 3H, J = 7.2Hz), 1.38 (m, 2H), 1.67 (m, 2H), 2.18 (m, 5H), 2.85 (m, 4H), 3.31 (m,2H), 4.03 (t, 3H, J = 6.6 Hz), 7.11 (d, 2H, J = 9 Hz), 7.78 (dd, 1H, J =9, 2.4 Hz), 7.95 (m, 3H), 8.29 (m, 1H), 8.96 (s, 1H) 93 493 1HNMR (600MHz, CDCl3, 25° C.): 0.94 (t, 3H, J = 7.2 Hz)), 1.45 (m, 2H), 1.74 (m,2H), 2.29 (q, 2H, J = 5.4 Hz), 6.84 (dd, 2H, J = 6.6, 1.8 Hz), 6.96 (d,1H, J = 1.2 Hz), 7.40 (d, 2H, J = 9 Hz), 7.74 (dd, 1H, J = 9, 1.8 Hz),8.14 (s, 1H), 8.32 (d, 1H, J = 3 Hz), 8.66 (s, 1H), 9.76 (s, 1H) 94 458¹HNMR (600 MHz, D₆-DMSO, 25° C.): 2.21 (m, 2H), 2.71 (m, 2H), 2.94 (m,4H), 3.83 (s, 3H), 7.13 (m, 2H), 7.89 (m, 1H), 7.96 (m, 1H), 8.48 (s,1H), 8.25 (m, 1H), 8.45 (m, 1 Hz), 9.03 (s, 1H) 95 441 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.16 (t, 3H, J = 7.8 Hz), 2.66 (q, 2H, J = 15 Hz),3.58 (q, 2H, J = 9.6 Hz), 3.81 (q, 2H, J = 10.2 Hz), 5.31 (t, 1H, J =4.8 Hz), 7.45 (d, 2H, J = 9 Hz), 7.78 (dd, 1H, J = 9, 1.8 Hz), 7.84 (m,1H), 7.96 (d, 1H, J = 9.6 Hz), 7.98 (d, 2H, J = 1.8 Hz), 8.22 (d, 1H, J= 2.4 Hz), 8.92 (s, 1H) 96 457 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 3.68(s, 3H), 3.79 (s, 3H), 3.82 (s, 3H), 4.02 (s, 3H), 6.19 (s, 1H), 7.06(dd, 2H, J = 21.6 Hz), 7.28 (dd, 1H, J = 8.4, 1.8 Hz), 7.63 (s, 1H),8.39 (s, 1H), 8.96 (s, 1H), 9.42 (s, 1H) 97 412 ¹HNMR (600 MHz, D₆-DMSO,25° C.): 3.84 (s, 3H), 7.09 (d, 2H, J = 9 Hz), 7.83 (d, 2H, J = 9 Hz),7.91 (d, 1H, J = 2.4 Hz), 8.48 (s, 1H), 8.50 (d, 1H, J = 9.6 Hz), 8.70(dd, 1H, J = 9, 2.4 Hz), 9.03 (s, 1H), 9.85 (s, 1H) 98 406 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 3.83 (s, 3H), 4.17 (s, 2H), 7.08 (dd, 1H, J =7.2, 1.8 Hz), 7.14 (d, 4H, J = 1.2 Hz), 7.62 (dd, 2H, J = 7.2, 1.8 Hz),8.01 (dd, 1H, J = 9, 1.8 Hz), 8.32 (d, 1H, J = 3 Hz), 8.40 (s, 1H), 9.01(s, 1H), 9.66 (s, 1H) 99 452 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 2.19 (m,5H), 2.66 (m, 2H), 2.89 (m, 8H), 3.82 (s, 3H), 4.24 (s, 2H), 7.12 (d,2H, J = 7.8 Hz), 7.68 (d, 1H, J = 7.2 Hz), 7.85 (d, 1H, J = 8.4 Hz),7.95 (d, 2H, J = 8.4 Hz), 8.23 (s, 1H), 8.92 (s, 1H) 100 579 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 1.17 (m, 9H), 1.73 (m, 2H), 2.67 (m, 4H), 2.82(m, 4H), 3.20 (m, 5H), 3.39 (m, 6H), 7.48 (d, 2H, J = 8.4 Hz), 7.84 (d,2H, J = 7.8 Hz), 7.96 (dd, 1H, J = 9.6, 1.8 Hz), 8.17 (m, 1H), 8.30 (d,1H, J = 9.6 Hz), 9.34 (s, 1H) 101 581 ¹HNMR (600 MHz, D₆-DMSO, 25° C.):1.16 (t, 3H, J = 7.8 Hz), 1.21 (m, 6H), 1.36 (m, 2H), 1.70 (m, 2H), 2.67(q, 2H, J = 15 Hz), 3.09 (m, 10H), 3.59 (m, 2H), 3.74 (m, 2H), 7.44 (d,2H, J = 8.4 Hz), 7.79 (d, 2H, J = 7.8 Hz), 7.95 (d, 1H, J = 15 Hz), 8.05(m, 1H), 8.30 (d, 1H, J = 9.6 Hz), 9.35 (s, 1H) 102 565 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.17 (t, 3H, J = 7.8 Hz), 1.23 (m, 3H), 1.76 (m, 6H),2.68 (q, 2H, J = 15 Hz), 2.97 (m, 2H), 3.07 (m, 2H), 3.34 (m, 6H), 7.46(d, 2H, J = 7.8 Hz), 7.81 (d, 2H, J = 7.8 Hz), 7.98 (d, 1H, J = 3 Hz),8.14 (m, 1H), 8.33 (d, 1H, J = 9.6 Hz), 9.41 (s, 1H) 103 536 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 1.16 (m, 9H), 1.73 (m, 2H), 2.68 (q, 2H, J = 15Hz), 2.92 (m, 4H), 3.34 (m, 6H), 7.45 (d, 2H, J = 8.4 Hz), 7.81 (d, 2H,J = 7.8 Hz), 7.99 (d, 1H, J = 9 Hz), 8.21 (m, 1H), 8.34 (d, 1H, J = 9Hz), 9.43 (s, 1H) 104 483 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.14 (t, 3H,J = 7.8 Hz), 1.25 (m, 2H), 1.35 (m, 2H), 1.51 (m, 2H), 1.96 (m, 1H),2.65 (q, 2H, J = 15 Hz), 3.34 (m, 2H), 3.70 (q, 2H, J = 12.6 Hz), 4.38(t, 1H, J = 1.8 Hz), 7.38 (t, 1H, J = 5.4 Hz), 7.46 (d, 2H, J = 8.4 Hz),7.79 (dd, 1H, J = 9, 1.2 Hz), 7.92 (d, 2H, J = 8.4 Hz), 7.97 (d, 1H, J =9.6 Hz), 8.18 (d, 1H, J = 1.8 Hz), 8.93 (s, 1H) 105 480 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.13 (t, 3H, J = 7.2 Hz), 1.56 (m, 5H), 2.59 (m, 2H),2.644 (q, 2H, J = 9 Hz), 2.90 (m, 2H), 7.45 (d, 2H, J = 7.8 Hz), 7.78(dd, 1H, J = 9, 3.6 Hz), 7.92 (m, 2H), 7.95 (d, 1H, J = 9 Hz), 8.36 (m,1H), 8.96 (s, 1H) 106 488 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J= 7.8 Hz), 2.69 (q, 2H, J = 15 Hz), 4.84 (d, 2H, J = 6 Hz), 7.27 (m,2H), 7.30 (d, 1H, J = 7.8 Hz), 7.55 (d, 1H, J = 8.4 Hz), 7.73 (m, 3H),7.85 (m, 1H), 8.70 (d, 1H, J = 9 Hz), 8.65 (d, 1H, J = 4.8 Hz), 9.08 (s,1H) 107 474 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (t, 3H, J = 7.8 Hz), ,2.74 (q, 2H, J = 15 Hz), 7.08 (s, 1H), 7.34 (d, 2H, J = 6.6 Hz), 7.40(d, 2H, J = 8.4 Hz), 7.54 (d, 2H, J = 6.6 Hz), 7.59 (d, 2H, J = 9.6 Hz),7.83 (d, 1H, J = 9.6 Hz), 8.39 (d, 1H, J = 9 Hz), 9.69 (s, 1H), 10.03(m, 2H) 108 447 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.19 (t, 3H, J = 7.8Hz), 2.63 (q, 2H, J = 15 Hz), 6.33 (m, 2H), 6.53 (m, 2H), 6.87 (m, 1H),7.15 (d, 2H, J = 8.4 Hz), 7.39 (d, 2H, J = 7.8 Hz), 7.68 (d, 1H, J = 7.8Hz), 8.26 (d, 1H, J = 9 Hz), 9.78 (s, 1H) 109 448 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.13 (t, 3H, J = 7.8 Hz), 2.63 (q, 2H, J = 15.6 Hz),6.70 (t, 1H, J = 2.4 Hz), 6.77 (m, 1H), 7.35 (d, 2H, J = 8.4 Hz), 7.54(d, 2H, J = 7.8 Hz), 7.83 (d, 1H, J = 1.8 Hz), 8.03 (dd, 1H, J = 9.6,2.4 Hz)), 8.18 (d, 1H, J = 2.4 Hz), 8.41 (d, 1H, J = 9 Hz), 9.71 (s, 1H)110 449 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.19 (t, 3H, J = 7.8 Hz), 2.65(q, 2H, J = 15 Hz), 6.73 (d, 1H, J = 1.8 Hz), 7.27 (m, 2H), 7.41 (d, 2H,J = 9 Hz), 7.75 (dd, 1H, J = 8.4, 1.8 Hz), 8.06 (d, 1H, J = 1.2 Hz),8.19 (d, 1H, J = 1.2 Hz), 8.32 (d, 1H, J = 9 Hz), 9.77 (s, 1H) 111 469¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.14 (t, 3H, J = 7.8 Hz), 1.39 (m,2H), 1.57 (m, 2H), 2.65 (q, 2H, J = 9 Hz), 3.73 (q, 2H, J = 12 Hz), 4.48(t, 1H, J = 5.4 Hz), 7.41 (t, 1H, J = 4.8 Hz), 7.46 (d, 2H, J = 7.8 Hz),7.79 (d, 1H, J = 3 Hz), 7.92 (d, 2H, J = 8.4 Hz), 7.97 (d, 1H, J = 9Hz), 8.18 (s, 1H), 8.93 (s, 1H) 112 499 ¹HNMR (600 MHz, CDC_(l3), 25°C.): 1.19 (t, 3H, J = 7.8 Hz), 1.50 (m, 1H), 2.57 (q, 2H, J = 15 Hz),6.57 (d, 1H, J = 1.8 Hz), 7.13 (m, 1H), 7.20 (d, 2H, J = 8.4 Hz), 7.43(d, 2H, J = 8.4 Hz), 7.51 (m, 2H), 7.75 (dd, 1H, J = 9, 1.8 Hz), 8.23(m, 1H), 8.37 (d, 1H, J = 9 Hz), 9.85 (s, 1H) 113 567 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.47 (m, 4H), 1.89 (m, 4H), 3.04 (m, 2H), 3.36 (m,4H), 3.43 (m, 2H), 3.85 (s, 3H), 7.14 (d, 2H, J = 9 Hz), 7.86 (d, 2H, J= 6.6 Hz), 7.96 (m, 1H), 8.13 (s, 1H), 8.30 (d, 1H, J = 9 Hz), 9.35 (s,1H) 114 511 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.65 (m, 10H), 2.61 (m,2H), 3.35 (m, 4H), 3.85 (s, 3H), 7.16 (d, 2H, J = 7.8 Hz), 7.90 (d, 2H,J = 7.2 Hz), 8.29 (d, 1H, J = 7.2 Hz), 8.56 (d, 1H, J = 7.8 Hz), 9.0 (m,1H), 9.38 (s, 1H) 115 506 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.55 (m,12H), 2.96 (m, 2H), 3.45 (m, 4H), 3.84 (s, 3H), 4.35 (s, 2H), 7.15 (d,2H, J = 8.4 Hz), 7.86 (d, 2H, J = 5.4 Hz), 7.90 (d, 1H, J = 7.8 Hz),8.19 (d, 1H, J = 2.4 Hz), 8.25 (s, 1H), 9.33 (s, 1H) 116 568 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 0.93 (t, 3H, J = 7.8 Hz), 1.42 (m, 4H), 1.47 (m,2H), 1.58 (m, 6H), 1.75 (m, 2H), 2.41 (m, 2H), 3.0 (m, 2H), 3.33 (m,4H), 3.78 (s, 3H), 3.83 (s, 3H), 4.14 (t, 3H, J = 6 Hz), 7.16 (d, 1H, J= 7.8 Hz), 7.31 (s, 1H), 7.38 (s, 1H), 7.44 (m, 1H), 7.57 (dd, 1H, J =9, 1.8 Hz), 8.05 (d, 1H, J = 9 Hz), 9.15 (s, 1H) 117 462 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.20 (t, 3H, J = 7.2 Hz), 2.28 (s, 3H), 2.66 (q, 2H, J =15.6 Hz), 6.41 (d, 1H, J = 0.6 Hz), 6.97 (s, 1H), 7.22 (d, 2H, J = 6.6Hz), 7.33 (s, 1H), 7.40 (d, 2H, J = 8.4 Hz), 7.73 (dd, 1H, J = 15, 2.4Hz), 8.30 (d, 1H, J = 9 Hz), 9.79 (s, 1H) 118 448 ¹HNMR (600 MHz, CDCl₃,25° C.): 1.18 (t, 3H, J = 7.8 Hz), 2.64 (q, 2H, J = 15 Hz), 6.84 (s,1H), 6.87 (d, J = 1.2 Hz), 7.21 (s, 1H), 7.22 (s, 1H), 7.24 (s, 1H),7.36 (s, 1H), 7.37 (s, 1H), 7.39 (s, 1H), 7.73 (dd, 1H, J = 9, 1.8 Hz),8.31 (d, 1H, J = 9.6 Hz), 9.79 (s, 1H) 119 593 ¹HNMR (600 MHz, D₆-DMSO,25° C.): 0.91 (t, 3H, J = 7.2 Hz)), 1.39 (m, 2H), 1.55 (m, 10H), 1.68(m, 2H), 2.45 (m, 4H), 3.06 (m, 2H), 3.22 (m, 2H), 4.05 (t, 2H, J-6.6Hz), 7.12 (d, 2H, J = 9 Hz), 7.82 (d, 2H, J = 8.4 Hz), 7.94 (d, 1H, J =8.4 Hz), 8.15 (s, 1H), 8.29 (d, 1H, J = 3 Hz), 9.36 (s, 1H) 120 588¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.39 (m, 6H), 1.84 (m, 6H), 2.83 (m,1H), 2.96 (m, 2H), 3.27 (m, 2H), 3.45 (m, 2H), 8.02 (m, 3H), 8.17 (m,2H), 8.21 (s, 1H), 8.37 (d, 1H, J = 9 Hz), 9.49 (s, 1H) 121 542 ¹HNMR(600 MHz, D₆-DMSO, 25° C.): 1.42 (m, 10H), 2.39 (m, 2H), 2.65 (s, 3H),3.05 (m, 2H), 3.34 (m, 4H), 3.78 (s, 3H), 7.17 (d, 1H, J = 7.2 Hz), 7.30(s, 1H), 7.48 (m, 1H), 7.78 (d, 1H, J = 1.2 Hz), 7.81 (dd, 1H, J = 9,1.8 Hz), 8.04 (d, 1H, J = 9 Hz), 9.19 (s, 1H) 122 556 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 1.55 (m, 8H), 2.55 (m, 4H), 3.12 (m, 2H), 3.51 (m,5H), 3.83 (s, 6H), 3.96 (s, 3H), 3.98 (s, 3H), 7.15 (d, 1H, J = 9 Hz),7.28 (m, 2H), 7.34 (m, 1H), 7.51 (s, 1H), 9.14 (s, 1H) 123 473 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.77 (t, 6H, J = 7.2 Hz), 0.97 (t, 3H, J = 7.2Hz), 1.51 (m, 2H), 1.80 (m, 2H), 3.36 (q, 2H, J = 13.8 Hz), 3.90 (s,3H), 3.92 (s, 3H), 4.02 (t, 3H, J = 6 Hz), 6.92 (d, 1H, J = 8.4 Hz),7.23 (d, 1H, J = 9 Hz), 7.41 (dd, 2H, J = 8.4, 3 Hz), 7.54 (dd, 1H, J =8.4, 1.8 Hz), 8.01 (dd, 1H, J = 9.6, 3 Hz), 9.29 (s, 1H) 124 503 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.77 (t, 6H, J = 7.2 Hz), 1.01 (m, 4H), 1.20(m, 4H), 2.55 (s, 3H), 3.32 (t, 4H, J = 7.2 Hz), 3.90 (s, 3H), 3.91 (s,3H), , 6.92 (d, 1H, J = 8.4 Hz), 7.39 (d, 1H, J = 1.8 Hz), 7.51 (dd, 1H,J = 8.4, 1.8 Hz), 7.60 (dd, 1H, J = 8.4, 1.8 Hz), 7.71 (d, 1H, J = 2.4Hz), 7.79 (d, 1H, J = 8.4 Hz), 9.26 (s, 1H) 125 452 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.20 (t, 3H, J = 7.8 Hz), 2.28 (s, 3H), 2.66 (q, 2H, J =15 Hz), 6.76 (d, 1H, J = 1.2 Hz), 7.27 (d, 2H, J = 8.4 Hz), 7.35 (d, 2H,J = 8.4 Hz), 7.81 (dd, 1H, J = 9.6, 1.8 Hz), 8.01 (s, 1H), 8.38 (d, 1H,J = 9 Hz), 9.18 (s, 1H), 9.79 (s, 1H) 126 482 ¹HNMR (600 MHz, CDCl₃, 25°C.): 1.20 (t, 3H, J = 7.8 Hz), 2.67 (q, 2H, J = 15 Hz), 2.90 (m, 4H),3.83 (m, 4H), 7.33 (d, 2H, J = 8.4 Hz), 7.54 (dd, 1H, J = 9, 1.8 Hz),7.82 (d, 2H, J = 8.4 Hz), 8.00 (d, 1H, J = 8.4 Hz), 8.50 (m, 1H), 9.04(s, 1H), 9.47 (s, 1H) 127 425 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t,3H, J = 7.2 Hz), 1.17 (t, 3H, J = 7.2 Hz), 1.64 (m, 4H), 1.76 (m, 1H),1.96 (m, 2H), 2.60 (t, 3H, J = 7.8 Hz), 2.67 (q, 2H, J = 15 Hz), 2.93(m, 2H), 3.86 (m, 2H), 7.23 (d, 2H, J = 7.8 Hz), 7.31 (d, 2H, J = 8.4Hz), 7.40 (d, 2H, J = 7.8 Hz), 7.66 (dd, 1H, J = 9, 1.8 Hz), 7.79 (d,2H, J = 9 Hz), 8.16 (s, 1H), 8.26 (d, 1H, J = 9.6 Hz), 9.47 (s, 1H) 128587 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J = 7.8 Hz), 1.18 (t,3H, J = 7.2 Hz), 1.40 (t, 3H, J = 7.2 Hz), 1.63 (m, 2H), 1.72 (m, 2H),2.04 (m, 2H), 2.60 (t, 2H, J = 7.8 Hz), 2.67 (q, 2H, J = 15 Hz), 3.06(m, 2H), 3.97 (t, 2H, J = 11.4 Hz), 4.41 (q, 2H, J = 14.4 Hz), 7.22 (d,2H, J = 8.4 Hz), 7.32 (d, 2H, J = 8.4 Hz), 7.42 (d, 2H, J = 8.4 Hz),7.80 (d, 2H, J = 8.4 Hz), 8.22 (d, 1H, J = 8.4 Hz), 8.37 (dd, 1H, J = 9,1.8 Hz), 9.11 (d, 1H, J = 1.2 Hz), 9.45 (s, 1H) 129 601 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.64 (m, 3H), 1.77 (m, 2H),2.10 (m, 2H), 2.60 (t, 2H, J = 7.8 Hz), 3.02 (m, 2H), 3.84 (s, 3H), 3.91(m, 2H), 6.97 (d, 2H, J = 9 Hz), 7.24 (d, 2H, J = 8.4 Hz), 7.44 (d, 2H,J = 8.4 Hz), 7.66 (dd, 1H, J = 9, 1.8 Hz), 7.85 (d, 2H, J = 8.4 Hz),8.16 (s, 1H), 8.28 (m, 1H), 9.38 (s, 1H) 130 552 ¹HNMR (600 MHz, CDCl₃,25° C.): 0.83 (m, 2H), 1.23 (t, 3H, J = 7.2 Hz), 1.43 (t, 3H, J = 7.2Hz), 1.75 (m, 11H), 2.71 (q, 2H, J = 15 Hz), 3.02 (m, 2H), 3.32 (m, 2H),349 (m, 2H), 4.43 (m, 2H), 7.35 (d, 2H, J = 7.2 Hz), 7.77 (d, 2H, J =7.8 Hz), 8.15 (m, 1H), 8.35 (d, 1H, J = 9 Hz), 8.88 (s, 1H), 9.30 (s,1H) 131 567 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.22 (m, 9H), 1.42 (t, 3H, J= 7.2 Hz), 1.90 (m, 2H), 2.70 (q, 2H, J = 15 Hz), 2.81 (m, 2H), 2.92 (m,2H), 2.97 (m, 6H), 3.05 (m, 2H), 3.42 (m, 2H), 4.41 (q, 2H, J = 13.8Hz), 7.35 (d, 2H, J = 8.4 Hz), 7.80 (d, 2H, J = 8.4 Hz), 8.14 (d, 1H, J= 8.4 Hz), 8.34 (dd, 1H, J = 9, 1.8 Hz), 9.00 (d, 1H, J = 1.2 Hz), 9.31(s, 1H) 132 568 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.23 (t, 3H, J = 7.8Hz), 1.43 (t, 3H, J = 7.2 Hz), 1.51 (t, 6H, J = 7.2 Hz), 1.79 (m, 2H),1.88 (m, 2H), 2.71 (q, 2H, J = 15 Hz), 3.31 (m, 2H), 3.34 (m, 2H), 3.41(m, 4H), 3.57 (m, 2H), 3.78 (m, 1H), 4.13 (m, 2H), 4.42 (q, 2H, J = 14.4Hz), 7.37 (d, 2H, J = 8.4 Hz), 7.79 (d, 2H, J = 8.4 Hz), 8.18 (d, 1H, J= 8.4 Hz), 8.34 (dd, 1H, J = 9, 1.8 Hz), 8.93 (d, 1H, J = 1.8 Hz), 9.32(s, 1H) 133 487 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.18 (t, 3H, J = 7.2Hz), 1.22 (t, 3H, J = 6.6 Hz), 2.61 (q, 2H, J = 15 Hz), 4.23 (m, 2H),7.11 (m, 1H), 7.19 (d, 2H, J = 8.4 Hz), 7.44 (d, 2H, J = 8.4 Hz), 7.50(m, 2H), 7.55 (d, 1H, J = 1.2 Hz), 8.23 (m, 1H), 8.36 (d, 1H, J = 8.4Hz), 8.47 (dd, 1H, J = 9, 1.8 Hz), 9.90 (s, 1H) 134 436 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.17 (t, 3H, J = 7.2 Hz), 1.31 (t, 3H, J = 7.2 Hz)2.63(q, 2H, J = 15.6 Hz), 4.32 (q, 2H, J = 10.8 Hz), 6.85 (s, 1H), 7.21 (d,2H, J = 7.8 Hz), 7.24 (s, 1H), 7.38 (d, 2H, J = 8.4 Hz), 7.43 (m, 1H),7.82 (d, 1H, J = 2.4 Hz), 8.28 (d, 1H, J = 9 Hz), 8.44 (dd, 1H, J = 9,1.8 Hz), 9.83 (s, 1H) 135 469 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.23 (m,3H), 1.43 (m, 3H), 1.81 (m, 4H), 2.72 (m, 2H), 3.14 (m, 2H), 3.31 (m,2H), 3.65 (m, 1H), 3.95 (m, 1H), 4.44 (m, 2H), 7.38 (m, 2H), 7.81 (m,2H), 8.16 (m, 1H), 8.34 (m, 1H), 8.97 (m, 1H), 9.19 (m, 1H) 136 5381HNMR (600 MHz, CDCl₃, 25° C.): 1.42 (t, 3H, J = 7.2 Hz), 1.56 (m, 2H),1.87 (m, 6H), 2.05 (m, 2H), 2.85 (m, 5H), 3.34 (m, 2H), 3.53 (m, 2H),3.87 (s, 3H), 4.43 (q, 2H, J = 8.4 Hz), 6.99 (d, 2H, J = 9 Hz), 7.80 (d,2H, J = 9 Hz), 8.12 (d, 1H, J = 9 Hz), 8.33 (dd, 1H, J = 8.4, 0.6 Hz),8.86 (s, 1H), 9.21 (s, 1H) 137 471 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.44(t, 3H, J = 6.6 Hz), 1.61 (m, 2H), 1.84 (m, 2H), 3.21 (m, 2H), 3.42 (m,2H), 3.72 (m, 1H), 3.89 (s, 3H), 4.44 (q, 2H, J = 13.8 Hz), 7.02 (d, 2H,J = 9 Hz), 7.87 (d, 2H, J = 12, 3 Hz), 8.22 (m, 1H), 8.35 (d, 1H, J = 9Hz), 9.01 (m, 1H), 9.08 (m, 1H) 138 554 ¹HNMR (600 MHz, CDCl₃, 25° C.):1.44 (t, 3H, J = 6.6 Hz), 2.02 (m, 10H), 2.23 (m, 2H), 2.50 (m, 2H),3.19 (m, 2H), 3.38 (m, 3H), 3.89 (s, 3H), 4.45 (q, 2H, J = 13.8 Hz),7.03 (d, 2H, J = 8.4 Hz), 7.82 (d, 2H, J = 8.4 Hz), 8.17 (d, 1H, J = 8.4Hz), 8.36 (d, 1H, J = 9 Hz), 8.81 (m, 1H), 9.17 (s, 1H) 139 569 ¹HNMR(600 MHz, CDCl₃, 25° C.): 1.32 (m, 6H), 1.43 (t, 3H, J = 7.2 Hz), 1.97(m, 2H), 2.89 (m, 2H), 2.98 (m, 2H), 3.05 (m, 8H), 3.41 (m, 2H), 3.46(m, 2H), 3.88 (s, 3H), 4.42 (q, 2H, J = 8.4 Hz), 7.01 (d, 2H, J = 9 Hz),7.85 (d, 2H, J = 9 Hz), 8.14 (d, 1H, J = 9 Hz), 8.33 (dd, 1H, J = 9, 1.8Hz), 9.02 (d, 1H, J = 1.8 Hz), 9.25 (s, 1H) 140 570 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.43 (m, 9H), 1.68 (m, 2H), 1.81 (m, 2H), 1.94 (m,2H)3.17 (m, 2H), 3.29 (m, 4H), 3.55 (m, 2H), 3.75 (m, 1H), 3.87 (s, 3H),4.07 (q, 2H, J = 4.2 Hz), 4.42 (q, 2H, J = 14.4 Hz), 7.01 (d, 2H, J = 9Hz), 7.83 (d, 2H, J = 9 Hz), 8.14 (d, 1H, J = 8.4 Hz), 8.33 (dd, 1H, J =8.4, 1.2 Hz), 8.94 (d, 1H, J = 1.2 Hz), 9.27 (s, 1H) 141 438 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.33 (t, 3H, J = 6.6 Hz), 3.82 (s, 3H), 4.34 (q,2H, J = 14.4 Hz), 6.86 (d, 2H, J = 9 Hz), 6.92 (m, 1H), 7.29 (m, 1H),7.41 (d, 2H, J = 8.4 Hz), 7.46 (m, 1H), 7.84 (d, 1H, J = 1.2 Hz), 8.30(d, 1H, J = 9 Hz), 8.46 (m, 1H), 9.85 (s, 1H) 142 489 ¹HNMR (600 MHz,CDCl₃, 25° C.): 1.25 (t, 3H, J = 7.2 Hz), 3.82 (s, 3H), 4.26 (m, 2H),6.85 (m, 2H), 7.47 (m, 4H), 7.93 (m, 2H), 8.26 (m, 1H), 8.38 (d, 1H, J =9 Hz), 8.49 (dd, 1H, J = 9, 1.2 Hz), 9.92 (s, 1H) 143 525 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.85 (m, 12H), 2.80 (m, 4H), 3.34 (m, 2H), 3.53 (m,2H), 3.88 (s, 3H), 4.01 (s, 3H), 7.00 (d, 2H, J = 9 Hz), 7.81 (d, 2H, J= 8.4 Hz), 8.14 (d, 1H, J = 8.4 Hz), 8.34 (d, 1H, J = 8.4 Hz), 8.87 (m,1H), 9.23 (s, 1H) 144 484 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.44 (t, 3H, J= 7.2 Hz), 1.62 (m, 2H), 2.16 (m, 2H), 2.57 (s, 3H), 2.92 (m, 4H), 3.42(m, 2H), 3.89 (s, 3H), 4.45 (q, 2H, J = 13.8 Hz), 7.03 (d, 2H, J = 9Hz), 7.88 (d, 2H, J = 8.4 Hz), 8.16 (d, 1H, J = 9 Hz), 8.36 (dd, 1H, J =8.4, 1.2 Hz), 8.94 (m, 1H), 9.15 (m, 1H) 145 619 ¹HNMR (600 MHz, CDCl₃,25° C.): 1.19 (t, 3H, J = 7.8 Hz), 2.53 (m, 2H), 2.64 (m, 4H), 3.45 (m,2H), 3.59 (m, 2H), 3.85 (s, 3H), 6.92 (d, 2H, J = 15 Hz), 7.24 (d, 2H, J= 8.4 Hz), 7.36 (d, 2H, J = 8.4 Hz), 7.63 (dd, 1H, J = 9, 1.8 Hz), 7.76(d, 2H, J = 8.4 Hz), 7.87 (s, 1H), 8.23 (d, 1H, J = 9.6 Hz), 9.57 (s,1H) 146 587 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.18 (t, 3H, J = 7.8 Hz),1.68 (m, 3H), 1.97 (m, 2H), 2.68 (q, 2H, J = 15 Hz), 2.97 (m, 2H), 3.86(s, 3H), 3.90 (m, 2H), 6.85 (dd, 1H, J = 8.4, 2.4 Hz), 7.06 (m, 2H),7.33 (m, 3H), 7.67 (dd, 1H, J = 9, 1.8 Hz), 7.80 (d, 2H, J = 8.4 Hz),8.14 (s, 1H), 8.30 (d, 1H, J = 9 Hz), 9.45 (s, 1H) 147 601 148 575 ¹HNMR(600 MHz, CDCl₃, 25° C.): 1.22 (t, 3H, J = 7.8 Hz), 1.27 (t, 3H, J = 7.2Hz), 1.45 (m, 2H), 2.55 (m, 2H), 2.69 (m, 4H), 3.87 (s, 3H), 4.34 (q,2H, J = 14.4 Hz), 6.94 (d, 2H, J = 9 Hz), 7.26 (d, 2H, J = 8.4 Hz), 7.41(d, 2H, J = 8.4 Hz), 7.79 (d, 2H, J = 7.8 Hz), 8.23 (d, 1H, J = 9 Hz),8.37 (dd, 1H, J = 9, 1.8 Hz), 8.83 (d, 1H, J = 1.8 Hz), 9.65 (m, 1H) 149575 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.19 (t, 3H, J = 7.8 Hz), 1.41 (t,3H, J = 7.2 Hz), 1.72 (m, 2H), 2.09 (m, 2H), 2.68 (q, 2H, J = 15.6 Hz),3.09 (m, 2H), 3.81 (s, 1H), 3.98 (m, 2H), 4.42 (q, 2H, J = 14.4 Hz),6.85 (dd, 1H, J = 7.8, 1.8 Hz), 7.08 (d, 1H, J = 7.8 Hz), 7.11 (m, 1H),7.33 (m, 3H), 7.81 (d, 2H, J = 8.4 Hz), 8.29 (m, 1H), 8.38 (dd, 1H, J =9.6, 1.8 Hz), 9.11 (s, 1H), 9.45 (m, 1H) 150 589 ¹HNMR (600 MHz, CDCl₃,25° C.): 1.75 (m, 2H), 2.11 (m, 2H), 3.04 (m, 2H), 3.85 (s, 3H), 3.86(s, 3H), 3.94 (m, 2H), 6.86 (m, 1H), 6.98 (d, 2H, J = 8.4 Hz), 7.10 (m,2H), 7.34 (t, 1H, J = 8.4 Hz), 7.67 (d, 1H, J = 9 Hz), 7.85 (d, 1H, J =9 Hz), 8.15 (m, 1H), 8.30 (m, 1H), 9.37 (s, 1H) 151 538 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.97 (t, 3H, J = 7.2 Hz)), 1.48 (m, 2H), 1.77 (m, 2H),2.18 (m, 2H), 2.62 (s, 3H), 3.08 (m, 4H), 3.50 (m, 4H), 4.03 (t, 2H, J =6.6 Hz), 7.02 (d, 2H, J = 9 Hz), 7.64 (dd, 1H, J = 7.8, 1.2 Hz), 7.85(d, 2H, J = 9 Hz), 8.16 (d, 2H, J = 9 Hz), 8.96 (m, 1H) 152 608 ¹HNMR(600 MHz, CDCl₃, 25° C.): 1.44 (t, 3H, J = 6.6 Hz), 1.92 (m, 2H), 2.22(m, 2H), 3.28 (m, 4H), 3.36 (m, 1H), 3.87 (s, 3H), 4.06 (m, 4H), 4.45(q, 2H, J = 14.4 Hz), 7.03 (dd, 2H, J = 9.6, 3 Hz), 7.81 (m, 2H), 8.17(d, 1H, J = 9 Hz), 8.35 (dd, 1H, J = 14.4, 1.2 Hz), 8.81 (m, 1H), 9.17(s, 1H) 153 558 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.88 (m, 4H), 2.05 (m,4H), 2.29 (m, 2H), 2.62 (s, 3H), 2.89 (m, 1H), 3.05 (m, 1H), 3.18 (m,2H), 3.32 (m, 2H), 3.51 (m, 2H), 3.88 (s, 3H), 3.96 (s, 3H), 6.98 (d,1H, J = 8.4 Hz), 7.32 (d, 1H, J = 7.8 Hz), 7.49 (dd, 1H, J = 9, 2.4 Hz),7.66 (dd, 1H, J = 9, 1.8 Hz), 7.74 (m, 1H), 8.00 (d, 1H, J = 8.4 Hz),8.89 (s, 1H) 154 488 ¹HNMR (600 MHz, CDCl₃, 25° C.): 2.19 (m, 2H), 2.60(s, 3H), 2.61 (s, 3H), 3.02 (m, 4H), 3.44 (m, 2H), 3.56 (m, 2H), 3.91(s, 3H), 3.96 (s, 3H), 6.99 (d, 1H, J = 8.4 Hz), 7.39 (d, 1H, J = 1.8Hz), 7.54 (dd, 1H, J = 9, 2.4 Hz), 7.63 (dd, 1H, J = 9, 1.8 Hz), 7.82(m, 1H), 7.99 (d, 1H, J = 3 Hz), 8.76 (m, 1H) 155 582 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.99 (t, 6H, J = 7.2 Hz), 1.37 (t, 3H, J = 7.2 Hz), 1.40(m, 8H), 1.90 (m, 4H), 3.00 (m, 4H), 3.07 (q, 4H, J = 15 Hz), 3.43 (m,1H), 3.87 (s, 3H), 4.44 (q, 2H, J = 12.6 Hz), 7.02 (dd, 2H, J = 12, 3Hz), 7.82 (m, 2H), 8.16 (d, 1H, J = 9 Hz), 8.35 (dd, 1H, J = 8.4, 1.8Hz), 8.80 (m, 1H), 9.20 (s, 1H) 156 558 ¹HNMR (600 MHz, CDCl₃, 25° C.):1.44 (t, 3H, J = 6.6 Hz), 1.92 (m, 2H), 2.22 (m, 2H), 3.28 (m, 4H), 3.36(m, 1H), 3.87 (s, 3H), 4.06 (m, 4H), 4.45 (q, 2H, J = 14.4 Hz), 7.03(dd, 2H, J = 9.6, 3 Hz), 7.81 (m, 2H), 8.17 (d, 1H, J = 9 Hz), 8.35 (dd,1H, J = 14.4, 1.2 Hz), 8.81 (m, 1H), 9.17 (s, 1H) 157 580 ¹HNMR (600MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J = 7.2 Hz), 1.42 (t, 3H, J = 7.2 Hz),1.46 (q, 2H, J = 9 Hz), 1.57 (m, 2H), 1.75 (m, 2H), 1.80 (m, 6H), 2.06(m, 2H), 2.86 (m, 5H), 3.34 (m, 2H), 3.51 (t, 2H, J = 7.2 Hz), 4.00 (t,2H, J = 6.6 Hz), 4.31 (q, 2H, J = 14.4 Hz), 6.97 (m, 2H), 7.78 (m, 2H),8.12 (d, 1H, J = 8.4 Hz), 8.32 (dd, 1H, J = 8.4, 1.2 Hz), 8.85 (s, 1H),9.20 (s, 1H) 158 526 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J =7.2 Hz), 1.43 (t, 3H, J = 7.2 Hz), 1.46 (m, 2H), 1.75 (m, 2H), 2.14 (m,2H), 2.55 (s, 3H), 2.86 (m, 4H), 3.39 (t, 2H, J = 6.6 Hz), 3.62 (m, 2H),4.01 (t, 2H, J = 6.6 Hz), 4.43 (q, 2H, J = 14.4 Hz), 7.00 (d, 2H, J = 9Hz), 7.84 (m, 2H), 8.14 (d, 1H, J = 8.4 Hz), 8.34 (dd, 1H, J = 8.4, 1.2Hz), 8.95 (s, 1H), 9.15 (m, 1H) 159 554 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.96 (t, 3H, J = 7.2 Hz), 1.45 (m, 4H), 1.73 (m, 10H), 2.55 (s, 3H),2.70 (m, 5H), 3.21 (m, 2H), 3.42 (t, 2H, J = 10.8 Hz), 3.99 (t, 2H, J =6.6 Hz), 6.95 (d, 2H, J = 9 Hz), 7.63 (dd, 1H, J = 9, 1.8 Hz), 7.77 (dd,3H, J = 7.2, 2.4 Hz), 7.99 (d, 1H, J = 9 Hz), 9.11 (m, 1H) 160 501 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.47 (m, 2H), 1.76(m, 2H), 2.08 (m, 2H), 2.54 (s, 3H), 2.61 (s, 3H), 2.87 (m, 4H), 3.36(m, 4H), 6.99 (d, 2H, J = 9 Hz), 7.62 (dd, 1H, J = 9, 1.8 Hz), 7.84 (d,2H, J = 8.4 Hz), 7.89 (m, 1H), 7.98 (d, 1H, J = 9 Hz), 8.99 (m, 1H) 161596 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J = 7.2 Hz), 1.42 (t,3H, J = 6.6 Hz), 1.46 (m, 2H), 1.75 (m, 2H), 1.85 (m, 4H), 2.00 (m, 4H),2.03 (m, 2H), 2.61 (m, 2H), 3.21 (m, 2H), 3.31 (m, 3H), 3.51 (t, 2H, J =11.4 Hz), 4.00 (t, 2H, J = 6.6 Hz), 4.44 (q, 2H, J = 14.4 Hz), 6.97 (m,2H), 7.78 (m, 2H), 8.12 (d, 1H, J = 8.4 Hz), 8.32 (dd, 1H, J = 8.4, 1.2Hz), 8.85 (s, 1H), 9.20 (s, 1H) 162 570 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.96 (t, 3H, J = 7.8 Hz), 1.47 (m, 2H), 1.76 (m, 9H), 2.00 (m, 2H), 2.24(m, 2H), 3.21 (m, 4H), 3.38 (m, 2H), 3.52 (m, 2H), 4.02 (m, 2H), 6.99(d, 2H, J = 9 Hz), 7.66 (d, 2H, J = 8.4 Hz), 7.75 (d, 2H, J = 9 Hz),8.03 (d, 1H, J = 9 Hz), 9.05 (m, 1H) 163 516 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.97 (t, 3H, J = 7.2 Hz), 1.47 (m, 2H), 1.78 (m, 2H), 2.29 (m, 2H),2.59 (s, 3H), 2.80 (s, 3H), 3.07 (m, 2H), 3.22 (m, 2H), 3.47 (m, 2H),3.70 (m, 2H), 4.04 (t, 2H, J = 6.6 Hz), 7.04 (d, 2H, J = 9 Hz), 7.86 (d,2H, J = 9 Hz), 8.00 (d, 1H, J = 8.4 Hz), 8.28 (d, 1H, J = 9 Hz), 8.54(m, 1H), 8.94 (m, 1H) 164 532 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t,3H, J = 7.2 Hz), 1.46 (m, 2H), 1.76 (m, 2H), 2.14 (m, 2H), 2.60 (s, 3H),2.97 (m, 2H), 3.05 (m, 2H), 3.16 (s, 3H), 3.50 (m, 2H), 3.60 (m, 2H),4.02 (t, 2H, J = 6.6 Hz), 7.01 (d, 2H, J = 9 Hz), 7.84 (m, 2H), 8.19(dd, 1H, J = 9, 1.8 Hz), 8.27 (d, 1H, J = 9 Hz), 9.08 (m, 1H), 9.18 (m,1H) 165 511 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.24 (m, 6H), 2.04 (m, 4H),2.56 (s, 3H), 2.93 (m, 2H), 3.43 (m, 8H), 3.89 (s, 3H), 7.03 (d, 2H, J =7.8 Hz), 7.77 (dd, 1H, J = 8.4, 1.8 Hz), 7.87 (d, 2H, J = 9 Hz), 8.16(d, 1H, J = 9 Hz), 8.22 (m, 1H), 9.08 (s, 1H) 166 554 ¹HNMR (600 MHz,D₆₋DMSO, 25° C.): 0.96 (t, 6H, J = 7.2 Hz), 1.22 (m, 2H), 1.81 (m, 2H),2.33 (s, 3H), 2.53 (m, 4H), 2.58 (t, 2H, J = 6.6 Hz), 2.63 (t, 2H, J =5.4 Hz), 3.22 (m, 2H), 3.26 (m, 2H), 3.37 (m, 2H), 3.84 (s, 3H), 7.15(d, 2H, J = 9 Hz), 7.87 (d, 2H, J = 9 Hz), 8.18 (d, 1H, J = 8.4 Hz),8.25 (dd, 1H, J = 9, 1.8 Hz)8.64 (t, 1H, J = 5.4 Hz), 8.74 (d, 1H, J =1.2 Hz), 9.36 (s, 1H) 167 570 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t,3H, J = 7.2 Hz), 1.47 (m, 2H), 1.77 (m, 2H), 2.01 (brm, 14H), 2.78 (m,2H), 2.82 (s, 3H), 3.34 (m, 2H), 3.54 (m, 2H), 4.02 (t, 2H, J = 5.4 Hz),7.07 (d, 2H, J = 9 Hz), 7.80 (m, 3H), 8.24 (d, 1H, J = 9 Hz), 8.53 (s,1H), 9.25 (s, 1H) 168 586 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J= 7.2 Hz), 1.47 (m, 2H), 1.76 (m, 2H), 2.07 (brm, 8H), 2.29 (m, 2H),2.84 (s, 3H), 3.08 (m, 2H), 3.35 (m, 4H), 3.59 (m, 2H), 4.02 (t, 2H, J =7.2 Hz), 7.02 (d, 2H, J = 9 Hz), 7.79 (m, 3H), 8.25 (d, 1H, J = 7.8 Hz),8.51 (m, 1H), 9.23 (s, 1H) 169 586 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96(t, 3H, J = 7.2 Hz), 1.47 (m, 2H), 1.58 (m, 2H), 1.76 (m, 2H), 1.94 (m,6H), 2.11 (m, 2H), 2.87 (m, 5H), 3.15 (s, 3H), 3.41 (m, 2H), 3.55 (m,2H), 4.01 (t, 2H, J = 6.6 Hz), 6.99 (d, 2H, J = 8.4 Hz), 7.80 (d, 2H, J= 9 Hz), 8.16 (dd, 1H, J = 8.4, 1.8 Hz), 8.25 (d, 1H, J = 8.4 Hz), 8.79(d, 1H, J = 1.8 Hz), 9.20 (s, 1H) 170 603 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.98 (t, 3H, J = 7.2 Hz), 1.49 (m, 2H), 1.77 (m, 2H), 2.02 (m, 2H),2.14 (m, 2H), 2.25 (m, 2H), 2.38 (m, 2H), 3.15 (s, 3H), 3.26 (m, 2H),3.40 (m, 2H), 3.63 (m, 2H), 4.01 (t, 2H, J = 6 Hz), 6.98 (d, 2H, J = 9Hz), 7.79 (d, 2H, J = 9 Hz), 8.16 (dd, 1H, J = 9, 1.8 Hz), 8.27 (d, 1H,J = 9 Hz), 8.76 (d, 1H, J = 0.6 Hz), 9.17 (m, 1H) 171 553 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.42 (t, 3H, J = 7.2 Hz), 1.74 (m, 2H), 1.85 (m,2H), 2.49 (s, 3H), 2.60 (m, 1H), 2.76 (m, 8H), 3.37 (m, 4H), 3.87 (s,3H), 4.42 (q, 2H, J = 13.2 Hz), 6.99 (d, 2H, J = 9 Hz), 7.81 (dd, 2H, J= 7.2, 2.4 Hz), 8.13 (d, 1H, J = 8.4 Hz), 8.32 (dd, 1H, J = 9, 1.8 Hz),8.94 (d, 1H, J = 1.8 Hz), 9.29 (m, 1H) 172 595 ¹HNMR (600 MHz, CDCl₃,25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.43 (t, 3H, J = 7.2 Hz), 1.48 (m,2H), 1.76 (m, 4H), 1.87 (m, 2H), 2.38 (s, 3H), 2.59 (m, 4H), 2.73 (m,4H), 3.33 (m, 2H), 3.46 (m, 2H), 4.0 (t, 2H, J = 6.6 Hz), 4.27 (q, 2H, J= 14.4 Hz), 6.96 (d, 2H, J = 9 Hz), 7.80 (dd, 2H, J = 7.2, 1.8 Hz),78.11 (d, 1H, J = 9 Hz), 8.32 (dd, 1H, J = 9, 1.8 Hz), 8.94 (d, 1H, J =1.2 Hz), 9.25 (m, 1H) 173 552 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.44 (t,3H, J = 7.2 Hz), 1.75 (m, 14H), 3.36 (m, 2H), 3.53 (m, 2H), 3.88 (s,3H), 4.45 (q, 2H, J = 13.8 Hz), 7.01 (d, 2H, J = 8.4 Hz), 7.81 (d, 2H, J= 9 Hz), 8.15 (d, 1H, J = 9 Hz), 8.35 (dd, 1H, J = 9, 1.8 Hz), 8.84 (s,1H), 9.18 (s, 1H) 174 554 ¹HNMR (600 MHz, CDCl₃, 25° C.): 1.44 (t, 3H, J= 6.6 Hz), 1.65 (m, 4H), 1.77 (m, 6H), 2.55 (m, 1H), 2.74 (m, 3H), 3.36(m, 2H), 3.48 (m, 2H), 3.88 (s, 3H), 4.44 (q, 2H, J = 14.4 Hz), 7.00 (d,2H, J = 8.4 Hz), 7.82 (d, 2H, J = 9 Hz), 8.13 (d, 1H, J = 9 Hz), 8.34(dd, 1H, J = 9, 1.8 Hz), 8.91 (s, 1H), 9.24 (s, 1H) 175 568 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.44 (t, 3H, J = 7.2 Hz), 1.78 (m, 6H), 2.03 (m,4H), 2.17 (m, 2H), 2.30 (m, 2H), 2.85 (m, 2H), 3.39 (m, 2H), 3.57 (m,3H), 3.89 (s, 3H), 4.46 (q, 2H, J = 14.4 Hz), 7.04 (d, 2H, J = 9 Hz),7.82 (d, 2H, J = 9 Hz), 8.18 (d, 1H, J = 9 Hz), 8.36 (dd, 1H, J = 9, 1.8Hz), 8.79 (m, 1H), 9.18 (m, 1H) 176 594 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.97 (t, 3H, J = 7.2 Hz), 1.44 (t, 3H, J = 7.2 Hz), 1.49 (m, 2H), 2.00(brm, 17H), 3.37 (m, 2H), 3.53 (m, 2H), 4.02 (t, 2H, J = 6.6 Hz), 4.45(q, 2H, J = 14.4 Hz), 6.99 (d, 2H, J = 9 Hz), 7.79 (d, 2H, J = 9 Hz),8.15 (d, 1H, J = 9 Hz), 8.35 (dd, 1H, J = 8.4, 1.2 Hz), 8.83 (m, 1H),9.16 (m, 1H) 177 596 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J =7.8 Hz), 1.44 (t, 3H, J = 6.6 Hz), 1.47 (m, 2H), 1.76 (m, 10H), 2.55 (m,1H), 2.73 (m, 3H), 3.35 (m, 8H), 3.50 (m, 2H), 3.93 (m, 1H), 4.01 (t,2H, J = 6.6 Hz), 4.43 (q, 2H, J = 14.4 Hz), 6.97 (d, 2H, J = 9 Hz), 7.80(d, 2H, J = 9 Hz), 8.12 (d, 1H, J = 8.4 Hz), 8.33 (dd, 1H, J = 8.4, 1.8Hz), 8.92 (m, 1H), 9.22 (s, 1H) 178 610 179 581 1HNMR (600 MHz, CDCl3,25° C.): 1.44 (t, 6H, J = 7.2 Hz), 1.62 (m, 2H), 2.00 (m, 6H), 2.93 (m,2H), 3.02 (m, 2H), 3.07 (m, 7H), 3.16 (m, 3H), 3.42 (m, 2H), 3.48 (m,2H), 3.89 (s, 3H), 4.42 (q, 2H, J = 14.4 Hz), 7.02 (dd, 2H, J = 7.8, 1.8Hz), 7.85 (dd, 2H, J = 7.2, 1.8 Hz), 8.14 (d, 1H, J = 9 Hz), 8.33 (dd,1H, J = 8.4, 1.8 Hz), 8.99 (d, 1H, J = 1.28 Hz), 9.20 (s, 1H) 180 567¹HNMR (600 MHz, CDCl₃, 25° C.): 1.43 (t, 6H, J = 7.2 Hz), 1.99 (m, 2H),2.13 (m, 4H), 2.92 (m, 2H), 3.02 (m, 2H), 3.18 (m, 2H), 3.27 (m, 2H),3.38 (m, 4H), 3.43 (m, 2H), 3.48 (m, 2H), 3.88 (s, 3H), 4.22 (q, 2H, J =14.4 Hz), 7.02 (d, 2H, J = 9 Hz), 7.84 (m, 2H), 8.14 (d, 1H, J = 8.4Hz), 8.33 (dd, 1H, J = 9, 1.8 Hz), 9.00 (s, 1H), 9.21 (s, 1H) 181 623¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.8 Hz), 1.44 (t, 3H,7.2 Hz), 1.47 (m, 2H), 1.64 (m, 2H), 1.77 (m, 2H), 2.00 (m, 6H), 3.00(m, 2H), 3.21 (m, 8H), 3.24 (m, 2H), 3.44 (m, 2H), 3.53 (m, 2H), 4.02(t, 2H, J = 6.6 Hz), 4.28 (q, 2H, J = 14.4 Hz), 7.01 (d, 2H, J = 9 Hz),7.83 (d, 2H, J = 9 Hz), 8.13 (d, 1H, J = 9 Hz), 8.33 (dd, 1H, J = 8.4,1.2 Hz), 8.96 (s, 1H), 9.14 (s, 1H) 182 609 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.96 (t, 6H, J = 7.2 Hz), 1.43 (t, 3H, J = 7.2 Hz), 1.46 (m, 2H),1.73 (m, 2H), 1.96 (m, 2H), 2.11 (m, 4H), 2.89 (m, 2H), 2.97 (m, 2H),3.14 (m, 2H), 3.23 (m, 2H), 3.55 (m, 4H), 3.42 (m, 2H), 3.47 (m, 2H),4.01 (t, 2H, J = 6.6 Hz), 4.20 (q, 2H, J = 1.8 Hz), 6.99 (d, 2H, J = 8.4Hz), 7.82 (d, 2H, J = 8.4 Hz), 8.13 (d, 1H, J = 8.4 Hz), 8.33 (dd, 1H, J= 9, 1.2 Hz)9.02 (s, 1H), 9.22 (s, 1H) 183 439 ¹HNMR (600 MHz, CDCl₃,25° C.): 1.33 (t, 3H, J = 7.2 Hz), 3.82 (s, 3H), 4.34 (q, 2H, J = 14.4Hz), 6.86 (dd, 2H, J = 7.2, 2.4 Hz), 7.43 (dd, 2H, J = 7.2, 1.2 Hz),7.90 (d, 1H, J = 1.8 Hz), 8.15 (s, 1H), 8.03 (d, 1H, J = 9 Hz), 8.46(dd, 1H, J = 9, 1.8 Hz), 8.66 (s, 1H), 9.81 (s, 1H) 184 439 ¹HNMR (600MHz, CDCl₃, 25° C.): 1.32 (t, 3H, J = 7.2 Hz), 3.82 (s, 3H), 4.34 (q,2H, J = 14.4 Hz), 6.89 (dd, 2H, J = 7.2, 2.4 Hz), 7.45 (dd, 2H, J = 7.2,1.2 Hz), 7.68 (d, 1H, J = 1.2 Hz), 8.07 (d, 1H, J = 1.2 Hz), 8.20 (d,1H, J = 1.2 Hz), 8.30 (d, 1H, J = 9 Hz), 8.46 (dd, 1H, J = 8.4, 1.8 Hz),9.79 (s, 1H) 185 440 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 1.27 (t, 3H, J =7.2 Hz), 3.84 (s, 3H), 4.31 (q, 2H, J = 13.2 Hz), 7.15 (dd, 2H, J = 9,1.8 Hz), 7.51 (d, 1H, J = 1.2 Hz), 7.69 (dd, 2H, J = 7.2, 1.8 Hz), 8.45(d, 1H, J = 3 Hz), 8.50 (dd, 1H, J = 9, 1.8 Hz), 9.83 (s, 1H), 10.01 (s,1H) 186 482 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.90 (t, 3H, J = 7.8 Hz),1.27 (t, 3H, J = 7.2 Hz), 1.39 (m, 2H), 1.68 (m, 2H), 4.06 (t, 2H, J =7.2 Hz)), 4.31 (q, 2H, J = 14.4 Hz), 7.14 (dd, 2H, J = 6.6, 1.8 Hz),7.51 (d, 1H, J = 1.8 Hz), 7.69 (dd, 2H, J = 7.2, 2.4 Hz), 8.45 (d, 1H, J= 9 Hz), 8.50 (dd, 1H, J = 9, 1.8 Hz), 9.83 (s, 1H), 10.01 (s, 1H) 187N/A ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.46 (m,2H), 1.77 (m, 2H), 2.62 (m, 4H), 3.47 (m, 4H), 4.01 (q, 2H, J = 6.6 Hz),6.99 (m, 2H), 7.66 (dd, 1H, J = 9, 2.4 Hz), 7.78 (m, 2H), 8.03 (m, 1H),8.23 (d, 1H, J = 9.6 Hz), 9.35 (s, 1H) 188 481 ¹HNMR (600 MHz, CDCl₃,25° C.): 0.94 (t, 3H, J = 7.2 Hz), 1.33 (t, 3H, J = 7.2 Hz), 1.43 (m,2H), 1.73 (m, 2H), 3.57 (t, 2H, J = 6.6 Hz), 4.34 (q, 2H, J = 14.4 Hz),6.84 (d, 2H, J = 9 Hz), 7.42 (d, 2H, J = 9 Hz), 7.90 (d, 1H, J = 1.8Hz), 8.15 (s, 1H), 8.30 (d, 1H, J = 9 Hz), 8.46 (dd, 1H, J = 9, 1.8 Hz),8.67 (s, 1H), 9.17 (s, 1H) 189 481 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.93(t, 3H, J = 7.2 Hz), 1.33 (t, 3H, J = 7.2 Hz), 1.42 (m, 2H), 1.72 (m,2H), 3.95 (t, 2H, J = 6.6 Hz), 4.33 (q, 2H, J = 14.4 Hz), 6.87 (d, 2H, J= 9 Hz), 7.44 (d, 2H, J = 9 Hz), 7.69 (d, 1H, J = 1.2 Hz), 7.63 (s, 1H),8.08 (s, 1H), 8.20 (s, 1H), 8.30 (d, 1H, J = 9 Hz), 8.47 (dd, 1H, J =8.4, 1.8 Hz), 9.80 (s, 1H) 190 494 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.94(t, 3H, J = 7.2 Hz), 1.34 (t, 3H, J = 7.2 Hz), 1.45 (m, 2H), 1.73 (m,2H), 2.31 (s, 3H), 3.95 (m), 4.35 (q, 2H, J = 14.4 Hz), 6.51 (s, 1H),6.83 (d, 2H, J = 9 Hz), 7.38 (d, 1H, J = 0.6 Hz), 7.41 (d, 2H, J = 9Hz), 7.92 (d, 1H, J = 1.2 Hz), 8.28 (d, 1H, J = 9 Hz), 8.44 (dd, 1H, J =8.4, 1.8 Hz), 9.84 (s, 1H) 191 515 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95(t, 3H, J = 7.8 Hz), 1.44 (t, 3H, J = 7.2 Hz)1.47 (m, 2H), 1.77 (m, 2H),2.66 (m, 4H), 3.56 (m, 4H), 4.01 (t, 2H, J = 6.6 Hz), 4.45 (q, 2H, J =14.4 Hz), 6.99 (dd, 2H, J = 7.2, 1.8 Hz), 7.79 (dd, 2H, J = 7.2, 2.4Hz), 8.19 (d, 1H, J = 8.4 Hz), 8.36 (dd, 1H, J = 9, 1.8 Hz), 8.97 (d,1H, J = 1.2 Hz), 9.38 (s, 1H) 192 540 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.96 (t, 3H, J = 7.8 Hz), 1.33 (d, 6H, J = 6.6 Hz), 1.47 (m, 2H), 1.77(m, 2H), 2.16 (m, 2H), 2.68 (m, 2H), 2.83 (s, 3H), 3.09 (m, 3H), 3.58(m, 3H), 4.02 (t, 2H, J = 6.6 Hz), 4.37 (m, 1H), 7.01 (d, 2H, J = 9 Hz),7.84 (d, 2H, J = 8.4 Hz), 8.15 (d, 1H, J = 9 Hz), 8.30 (d, 1H, J = 8.4Hz), 8.80 (s, 1H), 9.02 (m, 1H) 194 481 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.93 (t, 3H, J = 7.2 Hz), 1.32 (t, 3H, J = 7.2 Hz), 1.43 (m, 2H), 1.72(m, 2H), 3.95 (m, 2H), 4.33 (q, 2H, J = 14.4 Hz), 6.82 (d, 2H, J = 8.4Hz), 6.90 (s, 1H), 7.27 (s, 1H), 7.38 (d, 2H, J = 2.4 Hz), 7.44 (s, 1H),7.83 (s, 1H), 8.29 (d, 1H, J = 9 Hz), 8.44 (d, 1H, J = 9 Hz), 9.83 (m,1H) 195 531 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.97 (t, 3H, J = 7.8 Hz),1.44 (t, 3H, J = 7.2 Hz), 1.48 (m, 2H), 1.78 (m, 2H), 2.86 (m, 4H), 3.24(m, 2H), 4.03 (t, 2H, J = 6.6 Hz), 4.29 (m, 2H), 4.45 (q, 2H, J = 13.8Hz), 7.02 (d, 2H, J = 8.4 Hz), 7.80 (d, 2H, J = 9 Hz), 8.24 (d, 1H, J =9 Hz), 8.41 (dd, 1H, J = 9, 1.8 Hz), 8.95 (s, 1H), 9.21 (s, 1H) 196 547¹HNMR (600 MHz, CDCl₃, 25° C.): 0.97 (t, 3H, J = 7.2 Hz), 1.45 (t, 3H, J= 7.2 Hz), 1.48 (m, 2H), 1.78 (m, 2H), 3.13 (m, 4H), 3.78 (m, 4H), 4.04(t, 2H, J = 6.6 Hz), 4.46 (q, 2H, J = 14.4 Hz), 7.05 (d, 2H, J = 9 Hz),7.81 (d, 2H, J = 8.4 Hz), 8.26 (d, 1H, J = 9 Hz), 8.43 (dd, 1H, J = 9,1.8 Hz), 8.77 (d, 1H, J = 1.2 Hz), 9.17 (s, 1H) 197 543 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.97 (t, 3H, J = 7.2 Hz), 1.48 (m, 2H), 1.77 (m, 2H),2.84 (m, 4H), 3.10 (m, 2H), 4.02 (q, 2H, J = 6.6 Hz), 4.24 (m, 2H), 7.01(d, 2H, J = 9 Hz), 7.71 (dd, 1H, J = 9, 1.2 Hz), 7.78 (m, 2H), 8.04 (s,1H), 8.26 (d, 1H, J = 9.6 Hz), 9.16 (s, 1H) 198 559 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.8 Hz), 1.48 (m, 2H), 1.79 (m, 2H),3.06 (m, 4H), 3.75 (m, 4H), 4.04 (q, 2H, J = 6.6 Hz), 7.05 (dd, 2H, J =7.2, 2.4 Hz), 7.73 (dd, 1H, J = 9, 1.2 Hz), 7.80 (m, 3H), 8.27 (d, 1H, J= 9 Hz), 9.10 (s, 1H) 199 553 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t,6H, J = 7.2 Hz), 1.16 (m, 3H), 1.28 (m, 3H), 1.47 (m, 2H), 1.77 (m, 2H),2.08 (m, 2H), 2.54 (s, 3H), 3.00 (m, 4H), 3.25 (m, 2H), 3.40 (m, 2H),3.59 (m, 4H), 4.01 (t, 2H, J = 6 Hz), 7.00 (d, 2H, J = 9 Hz), 7.75 (dd,1H, J = 8.4, 1.2 Hz), 7.83 (d, 2H, J = 9 Hz), 8.14 (d, 1H, J = 8.4 Hz),8.23 (s, 1H), 9.02 (m, 1H) 200 542 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96(t, 6H, J = 7.2 Hz), 1.47 (m, 2H), 1.76 (m, 2H), 2.10 (m, 2H), 2.62 (s,3H), 3.53 (m, 4H), 3.68 (m, 2H), 3.85 (m, 2H), 4.01 (t, 2H, J = 6 Hz),7.0 (d, 2H, J = 9 Hz), 7.83 (d, 2H, J = 9 Hz), 7.96 (m, 1H), 8.15 (d,1H, J = 9 Hz), 8.37 (dd, 1H, J = 9, 1.8 Hz), 8.94 (s, 1H), 9.10 (s, 1H)201 608 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.13(m, 3H), 1.30 (m, 3H), 1.49 (m, 2H), 1.73 (m, 16H), 2.74 (m, 1H), 3.26(m, 4H), 3.50 (m, 2H), 3.61 (m, 2H), 4.01 (t, 2H, J = 6.6 Hz), 6.98 (d,2H, J = 9 Hz), 7.75 (dd, 1H, J = 8, 1.8 Hz), 7.78 (d, 2H, J = 9 Hz),8.09 (s, 1H), 8.17 (d, 1H, J = 8.4 Hz), 9.21 (m, 1H) 202 597 ¹HNMR (600MHz, CDCl₃, 25° C.): 0.94 (t, 3H, J = 7.2 Hz), 1.24 (m, 2H), 1.45 (m,4H), 1.61 (m, 2H), 1.75 (m, .2H), 1.94 (m, 6H), 2.19 (m, 3H), 2.81 (m,2H), 2.94 (m, 2H), 3.62 (m, 2H), 3.83 (m, 2H), 3.94 (t, 2H, J = 6.6 Hz),4.22 (m, 1H), 6.88 (d, 2H, J = 9 Hz), 7.74 (d, 2H, J = 7.8 Hz), 8.13 (m,1H), 8.41 (d, 1H, J = 8.4 Hz), 8.99 (s, 1H), 9.47 (m, 1H) 206 597 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.49 (m, 2H), 1.60(m, 2H), 1.78 (m, 2H), 1.92 (m, 4H), 2.20 (m, 2H), 2.62 (s, 3H), 3.01(m, 4H), 3.15 (m, 4H), 3.31 (m, 4H), 3.95 (m, 2H), 3.63 (m, 2H), 4.03(t, 2H, J = 6.6 Hz), 7.03 (d, 2H, J = 9 Hz), 7.64 (dd, 1H, J = 9, 1.8Hz), 7.73 (s, 1H), 7.82 (d, 2H, J = 9 Hz), 7.99 (d, 1H, J = 9 Hz), 8.76(s, 1H) 207 583 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2Hz), 1.47 (m, 2H), 1.76 (m, 2H), 1.83 (m, 6H), 2.05 (m, 2H), 2.59 (s,3H), 2.80 (m, 10H), 3.29 (m, 4H), 3.99 (t, 2H, J = 6.6 Hz), 6.96 (d, 2H,J = 9 Hz), 7.63 (dd, 1H, J = 8.4, 1.8 Hz), 7.82 (d, 2H, J = 9 Hz), 7.97(d, 1H, J = 1.2 Hz), 8.00 (d, 1H, J = 9 Hz), 9.21 (s, 1H) 208 587 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.47 (m, 2H), 1.50(m, 3H), 1.71 (m, 10H), 2.43 (m, 1H), 2.59 (m, 4H), 2.80 (s, 3H), 3.30(m, 2H), 3.42 (m, 2H), 3.86 (m, 1H), 4.01 (t, 2H, J = 6.6 Hz), 6.96 (d,2H, J = 7.2 Hz), 7.75 (dt, 1H, J = 9, 1.8 Hz), 7.79 (dd, 2H, J = 9, 1.8Hz), 8.22 (dd, 1H, J = 9, 1.8 Hz), 8.58 (dd, 1H, J = 11.4, 1.2 Hz), 9.31(d, 1H, J = 9.6 Hz) 209 613 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H,J = 7.8 Hz), 1.48 (m, 4H), 1.77 (m, 6H), 1.91 (m, 2H), 2.50 (m, 2H),2.74 (m, 4H), 2.80 (s, 3H), 2.85 (m, 6H), 3.36 (m, 2H), 3.41 (m, 2H),4.00 (t, 2H, J = 6.6 Hz), 6.98 (d, 2H, J = 9 Hz), 7.83 (d, 2H, J = 9Hz), 7.89 (dd, 1H, J = 9.6, 1.8 Hz), 8.25 (d, 1H, J = 8.4 Hz), 8.77 (d,1H, J = 1.2 Hz), 9.33 (s, 1H) 210 599 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.95 (t, 2H, J = 7.2 Hz), 1.46 (m, 2H), 1.76 (m, 2H), 1.83 (m, 4H), 2.72(m, 2H), 2.80 (, s, 3H), 2.82 (m, 6H), 3.55 (m, 2H), 3.42 (m, 2H), 4.00(t, 2H, J = 6.6 Hz), 6.97 (dd, 2H, J = 6.6, 1.8 Hz), 7.82 (dd, 2H, J =7.2, 3 Hz), 7.91 (dd, 1H, J = 8.4, 1.8 Hz), 8.25 (d, 1H, J = 9 Hz), 8.78(d, 1H, J = 1.8 Hz), 9.36 (s, 1H). 211 609 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.94 (t, 6H, J = 7.2 Hz), 1.42 (t, 3H, J = 7.2 Hz), 1.46 (m, 2H),1.76 (m, 6H), 2.75 (m, 2H), 2.79 (s, 3H), 2.82 (m, 2H), 2.95 (m, 2H),3.08 (m, 2H), 3.17 (m, 2H), 3.29 (m, 2H), 3.39 (m, 2H), 3.45 (m, 2H),4.00 (t, 2H, J = 6 Hz), 4.41 (d, 2H, J = 14.4 Hz), 6.97 (d, 2H, J = 9Hz), 7.77 (d, 2H, J = 7.2, 2.4 Hz), 8.11 (d, 1H, J = 9 Hz), 8.32 (dd,1H, J = 8.4, 1.2 Hz), 8.89 (d, 1H, J = 1.2 Hz), 9.18 (s, 1H) 212 582¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.8 Hz), 1.40 (t, 3H, J= 7.8 Hz), 1.48 (m, 2H), 1.72 (m, 4H), 1.87 (m, 2H), 2.53 (m, 1H), 2.62(m, 4H), 3.38 (m, 2H), 3.47 (m, 2H), 3.77 (m, 4H), 4.01 (t, 2H, J = 6.6Hz), 4.27 (q, 2H, J = 14.4 Hz), 6.96 (dd, 2H, J = 6.6, 1.8 Hz), 7.80(dd, 2H, J = 7.2, 2.4 Hz), 8.10 (d, 1H, J = 8.4 Hz), 8.32 (dd, 1H, J =8.4, 1.8 Hz), 8.94 (dd, 1H, J = 1.2 Hz), 9.21 (s, 1H). 213 675 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.43 (t, 3H, J = 6.6Hz), 1.48 (m, 2H), 1.72 (m, 4H), 1.83 (m, 2H), 2.66 (m, 1H), 2.82 (m,3H), 3.19 (m, 3H), 3.40 (m, 2H), 3.51 (m, 2H), 4.00 (t, 2H, J = 6.6 Hz),4.42 (q, 2H, J = 14.4 Hz), 6.89 (m, 2H), 6.96 (m, 4H), 7.82 (dd, 2H, J =7.2, 1.8 Hz), 8.11 (d, 1H, J = 8.4 Hz), 8.33 (dd, 1H, J = 9, 1.8 Hz),8.96 (s, 1H), 9.21 (s, 1H) 214 625 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96(t, 6H, J = 7.2 Hz), 1.43 (t, 2H, J = 7.2 Hz), 1.46 (m, 2H), 1.75 (m,4H), 1.88 (m, 2H), 2.62 (m, 2H), 2.69 (m, 2H), 2.77 (m, 7H), 3.38 (m,4H), 3.70 (m, 2H), 4.00 (t, 2H, J = 6.6 Hz), 4.42 (q, 2H, J = 13.2 Hz),6.97 (d, 2H, J = 9 Hz), 7.90 (dd, 2H, J = 11.4, 2.4 Hz), 8.11 (d, 1H, J= 9 Hz), 8.32 (dd, 1H, J = 8.4, 1.8 Hz), 8.94 (d, 1H, J = 1.2 Hz), 9.24(s, 1H). 215 672 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2Hz), 1.43 (t, 3H, J = 6.6 Hz), 1.47 (m, 2H), 1.76 (m, 2H), 1.85 (m, 4H),1.98 (m, 2H), 2.34 (m, 2H), 2.83 (m, 5H), 3.35 (m, 2H), 3.51 (m, 2H),4.00 (t, 2H, J = 6.6 Hz), 4.43 (q, 2H, J = 13.8 Hz), 6.97 (d, 2H, J = 9Hz), 7.27 (d, 1H, J = 7.2 Hz), 7.35 (d, 2H, J = 7.8 Hz), 7.54 (d, 2H, J= 7.2 Hz), 7.80 (m, 2H), 8.12 (d, 1H, J = 8.4 Hz), 8.33 (dd, 1H, J = 9,1.8 Hz), 8.94 (s, 1H), 9.22 (s, 1H) 216 663 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.92 (t, 6H, J = 7.8 Hz), 1.39 (t, 3H, J = 7.2 Hz), 1.43 (m, 2H),1.61 (m, 2H), 1.72 (m, 4H), 1.84 (m, 2H), 1.95 (m, 6H), 2.24 (m, 2H),2.45 (m, 2H), 2.72 (m, 1H), 3.07 (m, 6H), 3.20 (m, 2H), 3.31 (m, 2H),3.41 (m, 2H), 3.97 (t, 2H, J = 6.6 Hz), 4.39 (q, 2H, J = 13.8 Hz), 6.95(d, 2H, J = 9 Hz), 7.76 (d, 2H, J = 9 Hz), 8.09 (d, 1H, J = 8.4 Hz),8.29 (dd, 1H, J = 8.4, 1.8 Hz), 8.86 (d, 1H, J = 1.8 Hz), 9.19 (s, 1H).217 598 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.97 (t, 3H, J = 7.2 Hz), 1.43(t, 3H, J = 7.2 Hz), 1.46 (m, 2H), 1.76 (m, 8H), 2.72 (m, 3H), 3.03 (m,4H), 3.37 (m, 2H), 3.54 (m, 2H), 4.01 (t, 2H, J = 6.6 Hz), 4.44 (1, 2H,J = 14.4 Hz), 6.98 (d, 2H, J = 9 Hz), 7.79 (m, 2H), 8.13 (d, 1H, J = 9Hz), 8.34 (dd, 1H, J = 9, 1.8 Hz), 8.88 (m, 1H), 9.17 (m, 1H) 218 543¹HNMR (600 MHz, CDCl₃, 25° C.): 0.88 (t, 3H, J = 7.2 Hz), 1.29 (m, 4H),1.33 (m, 4H), 1.44 (m, 2H), 1.79 (m, 3H), 2, 13 (m, 2H), 2.62 (s, 6H),2.95 (m, 3H), 3.40 (m, 4H), 4.01 (t, 2H, J = 6 Hz), 7.01 (d, 2H, J = 9Hz), 7.63 (d, 1H, J = 9, 2.4 Hz), 7.85 (d, 3H, J = 9 Hz), 7.99 (d, 1H, J= 9 Hz), 8.96 (m, 1H). 219 596 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t,3H, J = 6.6 Hz), 1.26 (m, 6H), 1.40 (m, 2H), 1.51 (m, 2H), 1.69 (m, 8H),1.87 (m, 2H), 2.58 (s, 3H), 2.69 (m, 5H), 3.19 (m, 2H), 3.40 (m, 2H),3.97 (t, 2H, J = 6.6 Hz), 6.93 (m, 2H), 7.62 (dd, 1H, J = 8.4, 1.8 Hz),7.76 (m, 3H), 7.98 (d, 1H, J = 8.4 Hz), 9.11 (s, 1H). 220 558 ¹HNMR (600MHz, CDCl₃, 25° C.): 0.86 (t, 3H, J = 6.6 Hz), 1.26 (m, 4H), 1.35 (m,2H), 1.42 (m, 2H), 1.79 (m, 2H), 2, 43 (m, 2H), 2.80 (s, 3H), 2.84 (s,3H), 3.34 (m, 2H), 3.52 (m, 4H), 3.82 (m, 2H), 4.03 (t, 2H, J = 6 Hz),7.06 (dd, 2H, J = 7.2, 2.4 Hz), 7.86 (dd, 2H, J = 6.6, 1.8 Hz), 7.98(dd1H, J = 9, 1.8 Hz), 8.27 (d, 1H, J = 9 Hz), 8.43 (d, 1H, J = 1.8 Hz),8.72 (s, 1H). 221 612 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.86 (t, 3H, J =6.6 Hz), 1.26 (m, 6H), 1.41 (m, 2H), 1.55 (m, 2H), 1.77 (m, 2H), 1.86(m, 6H), 2.02 (m, 2H), 2.81 (m, 8H), 3.32 (m, 2H), 3.49 (m, 2H), 3.99(t, 2H, J = 6.6 Hz), 6.99 (d, 2H, J = 9 Hz), 7.79 (dd, 3H, J = 9, 1.8Hz), 8.22 (d, 1H, J = 9 Hz), 8.53 (d, 1H, J = 81.2 Hz), 9.26 (s, 1H).222 570.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.46(m, 2H), 1.52 (m, 6H), 1.78 (m, 4H), 1.90 (m, 2H), 2.55 (s, 3H), 2.65(m, 4H), 3.21 (m, 2H), 3.42 (m, 2H), 3.95 (m, 1H), 4.01 (t, 2H, J = 6.6Hz), 6.96 (d, 2H, J = 9 Hz), 7.64 (dd, 1H, J = 9, 1.8 Hz), 7.78 (m, 3H),8.01 (d, 1H, J = 9 Hz), 9.13 (s, 1H) 223 612.3 ¹HNMR (600 MHz, CDCl₃,25° C.): 0.87 (t, 3H, J = 7.2 Hz), 1.28 (m, 6H), 1.43 (m, 2H), 1.78 (m,6H), 1.95 (m, 2H), 2.19 (m, 4H), 2.60 (s, 3H), 2.73 (m, 2H), 3.10 (m,2H), 3.24 (m, 2H), 3.45 (t, 2H, J = 11.4 Hz), 3.92 (m, 1H), 3.99 (t, 2H,J = 6.6 Hz), 6.97 (d, 2H, J = 8.4 Hz), 7.65 (dd, 1H, J = 8.4, 1.2 Hz),7.77 (m, 3H), 8.01 (dd, 1H, J = 8.4 Hz), 9.07 (s, 1H). 225 485.1 ¹HNMR(600 MHz, CDCl₃, 25° C.): 1.43 (t, 3H, J = 7.2 Hz), 2.38 (s, 3H), 2.89(m, 8H), 3.82 (s, 3H), 4.41 (q, 2H, J = 14.4 Hz), 6.94 (d, 2H, J = 9Hz), 7.83 (dd, 2H, J = 6.6, 1.8 Hz), 7.90 (d, 1H, J = 9 Hz), 8.26 (dd,1H, J = 9, 1.8 Hz), 8.49 (s, 1H), 9.08 (s, 1H), 10.29 (d, 1H, J = 1.8Hz). 226 459.1 ¹HNMR (600 MHz, CDCl₃, 25° C.): 2.37 (s, 3H), 2.56 (s,3H), 2.67 (m, 4H), 2.94 (m, 4H), 3.82 (s, 3H), 6.93 (dd, 2H, J = 8.4,1.8 Hz), 7.56 (dd, 1H, J = 9, 2.4 Hz), 7.82 (d, 3H, J = 9 Hz), 8.26 (m,1H), 8.94 (s, 1H), 9.18 (d, 1H, J = 1.8 Hz). 227 475.1 ¹HNMR (600 MHz,CDCl₃, 25° C.): 2.35 (s, 3H), 2.56 (m, 2H), 2.74 (s, 3H), 2.87 (m, 6H),3.81 (s, 3H), 6.93 (d, 2H, J = 9 Hz), 7.72 (dd, 1H, J = 9, 2.4 Hz), 7.82(d, 2H, J = 9 Hz), 7.99 (d, 1H, J = 9 Hz), 8.44 (s, 1H), 9.05 (s, 1H),9.94 (d, 1H, J = 1.8 Hz). 228 491.1 ¹HNMR (600 MHz, CDCl₃, 25° C.): 2.41(s, 3H), 2.59 (m, 2H), 2.91 (m, 6H), 3.09 (s, 3H), 3.83 (s, 3H), 6.95(dd, 2H, J = 7.2, 2.4 Hz), 7.84 (dd, 2H, J = 7.2, 1.8 Hz), 8.04 (dd, 2H,J = 17.4, 8.4 Hz)8.59 (s, 1H), 9.12 (s, 1H), 10.34 (d, 1H, J = 1.8 Hz).229 556.2 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.8 Hz), 1.45(m, 2H), 1.62 (m, 2H), 1.75 (m, 2H), 1.81 (m, 2H), 2.44 (m, 1H), 2.59(m, 7H), 3.25 (m, 2H), 3.35 (m, 2H), 3.77 (m, 4H), 3.99 (t, 2H, J = 6.6Hz), 6.95 (d, 2H, J = 9 Hz), 7.64 (dd, 1H, J = 9, 1.8 Hz), 7.79 (m, 2H),7.86 (m, 1H), 8.00 (d, 1H, J = 8.4 Hz), 9.15 (s, 1H). 230 596.2 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.8 Hz), 1.45 (m, 2H), 1.62(m, 2H), 1.75 (m, 2H), 1.81 (m, 2H), 2.47 (m, 1H), 2.57 (m, 12H), 3.23(m, 2H), 3.38 (m, 2H), 3.64 (t, 2H, J = 9 Hz), 4.01 (t, 2H, J = 6.6 Hz),6.95 (d, 2H, J = 9 Hz), 7.64 (dd, 1H, J = 9, 1.8 Hz), 7.79 (d, 2H, J =8.4 Hz), 7.85 (d, 1H, J = 1.2 Hz), 8.00 (d, 1H, J = 9 Hz), 9.15 (m, 1H).231 637 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J = 7.8 Hz), 1.46(m, 2H), 1.62 (m, 4H), 1.75 (m, 6H), 1.93 (m, 4H), 2.13 (m, 2H), 2.31(m, 2H), 2.73 (m, 1H), 2.89 (m, 3H), 3.09 (m, 2H), 3.18 (m, 2H), 3.92(m, 2H), 3.99 (t, 2H, J = 6 Hz), 6.94 (dd, 2H, J = 11.4, 3 Hz), 7.63(dd, 1H, J = 9, 1.8 Hz), 7.76 (m, 3H), 7.99 (d, 1H, J = 2.4 Hz), 9.12(m, 1H). 232 646.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2Hz), 1.41 (m, 2H), 1.63 (m, 4H), 1.71 (m, 2H), 1.83 (m, 4H), 2.21 (m,2H), 2.60 (s, 3H), 2.76 (m, 2H), 2.88 (m, 2H), 3.24 (m, 2H), 3.42 (m,2H), 4.00 (t, 3H, J = 6.6 Hz), 6.95 (m, 2H), 7.28 (m, 1H), 7.36 (t, 2H,J = 8.4 Hz), 7.54 (m, 2H), 7.64 (dd, 1H, J = 9, 1.8 Hz), 7.80 (m, 2H),7.87 (m, 1H), 8.01 (d, 1H, J = 8.4 Hz), 9.16 (m, 1H). 233 649.2 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.46 (m, 2H), 1.68(m, 2H), 1.77 (m, 2H), 1.80 (m, 2H), 2.56 (m, 1H), 2.59 (s, 3H), 2.78(m, 4H), 3.18 (m, 4H), 3.26 (m, 2H), 3.39 (m, 2H), 4.00 (t, 2H, J = 6.6Hz).6.89 (m, 2H), 6.96 (m, 3H), 7.64 (d, 1H, J = 9 Hz), 7.80 (d, 2H, J =9 Hz), 7.87 (s, 1H), 8.00 (d, 1H, J = 9 Hz), 9.15 (s, 1H). 234 583.2¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J = 7.2 Hz), 1.46 (m, 2H),1.58 (m, 2H), 1.75 (m, 4H), 2.10 (m, 2H), 2.58 (s, 3H), 2.61 (s, 3H),2.91 (m, 7H), 3.18 (m, 2H), 3.40 (m, 2H), 4.00 (t, 2H, J = 6.6 Hz), 6.95(d, 2H, J = 8.4 Hz), 7.63 (dd, 1H, J = 8.4, 1.8 Hz), 7.76 (d, 3H, J = 9Hz), 8.00 (d, 1H, J = 9 Hz), 9.10 (m, 1H). 235 572.2 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.8 Hz), 1.46 (m, 2H), 1.70 (m, 2H),1.75 (m, 2H), 1.86 (m, 2H), 2.50 (m, 1H), 2.61 (m, 4H), 2.80 (s, 3H),3.31 (m, 2H), 3.48 (m, 2H), 3.75 (m, 4H), 4.00 (t, 2H, J = 6.6 Hz), 6.96(dd, 2H, J = 7.2, 1.8 Hz), 7.77 (m, 3H), 8.21 (d, 1H, J = 9 Hz), 8.58(d, 1H, J = 1.8 Hz), 9.27 (s, 1H). 236 615.3 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.96 (t, 3H, J = 7.2 Hz), 1.48 (m, 2H), 1.73 (m, 4H), 1.85 (m, 2H),2.05 (m, 4H), 2.52 (m, 1H), 2.58 (m, 6H), 2.80 (s, 3H), 3.34 (m, 2H),3.45 (m, 2H), 3.63 (t, 2H, J = 5.4 Hz), 4.00 (t, 2H, J = 6.6 Hz), 6.96(d, 2H, J = 8.4 Hz), 7.77 (m, 3H), 8.21 (d, 1H, J = 8.4 Hz), 8.58 (d,1H, J = 1.8 Hz), 9.27 (s, 1H). 237 653.3 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.94 (t, 3H, J = 7.2 Hz), 1.44 (m, 4H), 1.65 (m, 12H), 1.93 (m, 2H),2.44 (m, 1H), 2.54 (m, 1H), 2.65 (m, 4H), 2.79 (s, 3H), 3.05 (m, 2H),3.29 (m, 2H), 3.43 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 6.95 (d, 2H, J = 9Hz), 7.76 (m, 3H), 8.20 (d, 1H, J = 9 Hz), 8.55 (d, 1H, J = 1.8 Hz),9.27 (s, 1H). 238 662.2 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t, 6H, J =7.2 Hz), 1.46 (m, 2H), 1.75 (m, 6H), 1.91 (m, 2H), 2.03 (m, 2H), 2.19(m, 2H), 2.67 (m, 1H), 2.76 (m, 1H), 2.79 (s, 3H), 2.90 (m, 2H), 3.32(m, 2H), 3.49 (m, 2H), 4.00 (t, 2H, J = 6 Hz), 6.97 (d, 2H, J = 9 Hz),7.25 (m, 1H), 7.33 (m, 2H), 7.53 (m, 2H), 7.78 (m, 3H), 8.21 (d, 1H, J =8.4 Hz), 8.58 (d, 1H, 1.8 Hz), 9.27 (s, 1H). 239 665.2 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.95 (t, 3H, J = 7.8 Hz), 1.24 (m, 2H), 1.75 (m, 4H),1.89 (m, 2H), 2.59 (m, 1H), 2.79 (m, 6H), 3.13 (m, 4H), 3.25 (m, 2H),3.49 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 6.87 (m, 2H), 6.94 (m, 4H), 7.77(m, 3H), 8.21 (d, 1H, J = 9 Hz), 8.59 (d, 1H, J = 1.8 Hz), 9.26 (s, 1H).240 599.2 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J = 7.2 Hz), 1.46(m, 2H), 1.64 (m, 2H), 1.75 (m, 4H), 1.90 (m, 2H), 2.44 (m, 2H), 2.37(m, 2H), 2.76 (m, 2H), 2.79 (s, 3H), 2.85 (m, 4H), 3.26 (m, 2H), 3.46(m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 6.95 (m, 2H), 7.75 (m, 3H), 8.21 (d,1H, J = 9 Hz), 8.57 (d, 1H, J = 1.8 Hz), 9.30 (s, 1H). 241 599.3 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.96 (t, 3H, J = 7.2 Hz), 1.47 (m, 2H), 1.63(m, 2H), 1.76 (m, 4H), 1.84 (m, 2H), 2.40 (s, 3H), 2.65 (m, 4H), 2.72(m, 1H), 2.80 (s, 3H), 2.83 (m, 4H), 3.24 (m, 2H), 3.46 (m, 2H), 4.00(t, 2H, J = 6.6 Hz), 6.95 (d, 2H, J = 9 Hz), 7.77 (m, 3H), 8.23 (d, 1H,J = 8.4 Hz), 8.57 (d, 1H, J = 1.8 Hz), 9.33 (s, 1H). 242 543.2 ¹HNMR(600 MHz, CDCl₃, 25° C.): 1.05 (t, 6H, J = 7.2 Hz), 2.15 (m, 2H), 2.58(s, 3H), 2.60 (s, 3H), 2.63 (q, 4H, J = 14.4 Hz), 2.86 (m, 2H), 2.98 (m,2H), 3.07 (m, 2H), 3.35 (m, 2H), 3.53 (m, 2H), 3.76 (t, 2H, J = 7.2 Hz),4.11 (t, 2H, J = 6 Hz), 7.02 (d, 2H, J = 9 Hz), 7.62 (dd, 1H, J = 8.4,1.8 Hz), 7.81 (m, 3H), 7.98 (d, 1H, J = 2.4 Hz), 8, 87 (s, 1H). 243572.2 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J = 7.2 Hz), 1.47 (m,2H), 1.61 (m, 2H), 1.76 (m, 2H), 2.58 (s, 3H), 2.69 (m, 4H), 2.88 (m,5H), 3.17 (m, 4H), 3.39 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 6.94 (d, 2H,J = 9 Hz), 7.63 (dd, 1H, J = 9, 1.8 Hz), 7.77 (m, 3H), 7.99 (d, 1H, J =9 Hz), 9.14 (m, 1H). 244 630.2 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.96 (t,3H, J = 7.2 Hz), 1.43 (t, 3H, J = 7.2 Hz), 1.47 (m, 2H), 1.76 (m, 2H),2.05 (m, 2H), 2.46 (m, 2H), 2.91 (m, 2H), 3.31 (m, 2H), 3.46 (m, 2H),3.55 (m, 4H), 3.82 (m, 2H), 4.00 (m, 2H), 4.20 (t, 2H, J = 12 Hz), 4.43(q, 2H, J = 14.4 Hz), 6.98 (d, 2H, J = 3 Hz), 7.79 (d, 2H, J = 3 Hz),8.16 (d, 1H, J = 9 Hz), 8.35 (dd, 1H, J = 8.4, 1.2 Hz), 8.83 (s, 1H),9.17 (s, 1H). 245 588.1 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.95 (t, 3H, J =7.2 Hz), 1.46 (m, 2H), 1.74 (m, 2H), 1.96 (m, 2H), 2.80 (s, 3H), 2.69(m, 4H), 2.92 (m, 3H), 3.28 (m, 2H), 3.34 (m, 2H), 3.43 (m, 2H), 3.48(m, 2H), 4.00 (t, 2H, J = 6.6 Hz), 6.97 (d, 2H, J = 9 Hz), 7.75 (dd, 1H,J = 9, 1.8 Hz), 7.77 (m, 2H), 8.23 (d, 1H, J = 9 Hz), 8.59 (d, 1H, J =1.2 Hz), 9.30 (m, 1H). 246 611.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.87(t, 3H, J = 7.2 Hz), 1.27 (m, 7H), 1.41 (m, 2H), 1.64 (m, 2H), 1.76 (m,4H), 2.34 (s, 3H), 2.49 (m, 4H), 2.55 (s, 3H), 2.68 (m, 4H), 3.21 (m,2H), 3.37 (m, 2H), 3.98 (t, 2H, J = 6.6 Hz), 6.94 (d, 2H, J = 9 Hz),7.63 (dd, 1H, J = 8.4, 1.8 Hz), 7.78 (d, 2H, J = 8.4 Hz), 7.83 (d, 1H, J= 1.2 Hz), 7.99 (d, 1H, J = 3 Hz), 9.15 (m, 1H). 247 612.3 ¹HNMR (600MHz, CDCl₃, 25° C.): 0.87 (t, 3H, J = 6.6 Hz), 1.29 (m, 7H), 1.41 (m,2H), 1.57 (m, 5H), 1.70 (m, 6H), 2.47 (m, 2H), 2.59 (s, 3H), 2.63 (m,3H), 3.20 (m, 2H), 3.40 (m, 2H), 3.87 (m, 1H), 3.99 (t, 2H, J = 6.6 Hz),6.95 (d, 2H, J = 9 Hz), 7.63 (d, 1H, J = 10.2 Hz), 7.76 (m, 3H), 8.00(d, 1H, J = 9 Hz), 9.16 (m, 1H). 248 639.3 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.87 (t, 3H, J = 6.6 Hz), 1.30 (m, 9H), 1.43 (m, 2H), 1.53 (m, 2H),1.79 (m, 6H), 2.04 (m, 2H), 2.61 (s, 3H), 2.78 (m, 5H), 2.98 (m, 6H),3.34 (m, 2H), 4.00 (t, 2H, J = 6.6 Hz), 6.99 (d, 2H, J = 9 Hz), 7.63(dd, 1H, J = 8.4, 1.2 Hz), 7.82 (m, 3H), 7.99 (d, 1H, J = 9 Hz), 8.96(m, 1H). 249 625.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.86 (t, 3H, J = 6.6Hz), 1.21 (m, 6H), 1.41 (m, 2H), 1.59 (m, 2H), 1.75 (m, 4H), 2.04 (m,2H), 2.56 (s, 3H), 2.58 (s, 3H), 2.73 (m, 1H), 2.88 (m, 8H), 3.18 (m,2H), 3.04 (m, 2H), 3.98 (t, 2H, J = 6 Hz), 6.94 (d, 2H, J = 9 Hz), 7.63(dd, 1H, J = 8.4, 1.8 Hz), 7.76 (m, 3H), 8.00 (d, 1H, J = 9 Hz), 9.11(m, 1H). 250 641 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.87 (t, 3H, J = 6.6Hz), 1.29 (m, 6H), 1.42 (m, 2H), 1.64 (m, 2H), 1.77 (m, 6H), 2.46 (m,1H), 2.57 (m, 11H), 3.23 (m, 2H), 3.37 (t, 2H, J = 10.8 Hz), 3.63 (t,2H, J = 11.4 Hz), 3.98 (t, 2H, J = 6.6 Hz), 6.95 (d, 2H, J = 9 Hz), 7.63(dd, 1H, J = 9, 2.4 Hz), 7.79 (d, 2H, J = 9 Hz), 7.85 (d, 1H, J = 1.8Hz), 7.99 (d, 1H, J = 8.4 Hz), 9.14 (s, 1H). 251 680 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.86 (t, 3H, J = 6.6 Hz), 1.25 (m, 6H), 1.40 (m, 2H),1.58 (m, 4H), 1.76 (m, 6H), 1.91 (m, 4H), 2.12 (m, 2H), 2.28 (m, 2H),2.56 (m, 1H), 2.58 (s, 3H), 2.76 (m, 5H), 3.08 (m, 2H), 3.19 (m, 2H),3.39 (t, 2H, J = 10.8 Hz), 3.98 (t, 2H, J = 6.6 Hz), 6.94 (d, 2H, J = 9Hz), 7.63 (dd, 1H, J = 9, 1.8 Hz), 7.77 (m, 3H), 7.99 (d, 1H, J = 3 Hz),9.11 (s, 1H). 252 529.2 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.87 (t, 3H, J =7.2 Hz), 1.28 (m, 6H), 1.41 (m, 2H), 1.77 (m, 2H), 2.35 (s, 3H), 2.44(m, 4H), 2.59 (s, 3H), 3.29 (m, 4H), 3.98 (t, 2H, J = 6.6 Hz), 6.94 (dd,2H, J = 7.2, 2.4 Hz), 7.65 (dd, 1H, J = 8.4, 1.8 Hz), 7.79 (dd, 2H, J =7.2, 1.8 Hz), 7.92 (d, 1H, J = 1.8 Hz), 8.03 (d, 1H, J = 9 Hz), 9.26 (s,1H). 253 627.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz),1.27 (m, 7H), 1.40 (m, 2H), 1.75 (m, 4H), 1.84 (m, 2H), 2.49 (s, 3H),2.59 (m, 1H), 2.78 (s, 3H), 2.82 (m, 6H), 3.34 (m, 4H), 3.98 (t, 2H, J =6.6 Hz), 6.95 (d, 2H, J = 9 Hz), 7.73 (dd, 1H, J = 8.4, 1.8 Hz), 7.78(d, 2H, J = 8.4 Hz), 8.21 (d, 1H, J = 8.4 Hz), 8.58 (d, 1H, J = 7.8 Hz),9.32 (m, 1H). 254 628.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.86 (t, 3H, J =6.6 Hz), 1.29 (m, 7H), 1.41 (m, 2H), 1.63 (m, 5H), 1.77 (m, 6H), 2.57(m, 3H), 2.73 (m, 5H), 2.80 (d, 3H, J = 1.8 Hz), 3.32 (m, 2H), 3.43 (m,2H), 3.94 (m, 1H), 3.99 (t, 2H, J = 6.6 Hz), 6.97 (d, 2H, J = 9 Hz),7.75 (dt, 1H, J = 9, 1.8 Hz), 7.79 (dd, 2H, J = 9, 1.2 Hz), 8.22 (dd,1H, J = 8.4, 1.2 Hz), 8.57 (dd, 1H, J = 9, 1.2 Hz), 9.28 (d, 1H, J = 1.2Hz). 255 655.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.86 (t, 3H, J = 6.6 Hz),1.26 (m, 7H), 1.41 (m, 2H), 1.56 (m, 2H), 1.84 (m, 3H), 1.93 (m, 2H),2.81 (s, 3H), 2.88 (m, 11H), 3.02 (m, 3H), 3.41 (m, 2H), 3.43 (m, 2H),3.99 (t, 2H, J = 6.6 Hz), 6.99 (d, 2H, J = 9 Hz), 7.63 (dd, 1H, J = 8.4,1.2 Hz), 7.82 (m, 3H), 7.99 (d, 1H, J = 9 Hz), 8.96 (m, 1H). 256 641.3¹HNMR (600 MHz, CDCl₃, 25° C.): 0.86 (t, 3H, J = 6.6 Hz), 1.26 (m, 6H),1.39 (m, 2H), 1.63 (m, 2H), 1.75 (m, 4H), 1.84 (m, 2H), 2.25 (m, 3H),2.39 (s, 3H), 2.66 (m, 4H), 2.79 (s, 3H), 2.84 (m, 4H), 3.23 (m, 2H),3.44 (m, 2H), 3.98 (t, 2H, J = 6 Hz), 6.94 (d, 2H, J = 9 Hz), 7.63 (dd,1H, J = 8.4, 1.8 Hz), 7.76 (m, 3H), 8.00 (d, 1H, J = 9 Hz), 9.11 (m,1H). 257 657.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 6.6 Hz),1.25 (m, 6H), 1.40 (m, 2H), 1.73 (m, 4H), 1.85 (m, 2H), 2.50 (m, 5H),2.61 (m, 2H), 2.68 (m, 7H), 2.78 (s, 3H), 3.32 (m, 2H), 3.40 (m, 2H),3.97 (t, 2H, J = 6.6 Hz), 6.95 (d, 2H, J = 9 Hz), 7.74 (dd, 1H, J =14.4, 7.2 Hz), 7.78 (d, 2H, J = 9 Hz), 8.19 (d, 1H, J = 9 Hz), 8.58 (d,1H, J = 1.2 Hz), 9.24 (s, 1H). 258 695.3 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.84 (t, 3H, J = 6.6 Hz), 1.25 (m, 6H), 1.39 (m, 2H), 1.54 (m, 2H), 1.69(m, 8H), 1.89 (m, 4H), 2.09 (m, 2H), 2.25 (m, 2H), 2.59 (m, 1H), 2.73(m, 2H), 2.78 (s, 3H), 2.85 (m, 3H), 3.09 (m, 2H), 3.28 (m, 2H), 3.42(m, 2H), 3.97 (t, 2H, J = 6.6 Hz), 6.94 (d, 2H, J = 9 Hz), 7.73 (dd, 1H,J = 9, 1.8 Hz), 7.76 (d, 2H, J = 9 Hz), 8.19 (d, 1H, J = 3 Hz), 8.55 (d,1H, J = 1.8 Hz), 9.26 (s, 1H). 259 544.2 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.86 (t, 3H, J = 7.2 Hz), 1.26 (m, 6H), 1.40 (m, 2H), 1.76 (m, 2H), 2.38(s, 3H), 2.55 (m, 4H), 2.79 (s, 3H), 3.39 (m, 4H), 3.98 (t, 2H, J = 6.6Hz), 6.95 (dd, 2H, J = 7.2, 1.8 Hz), 7.80 (dd, 1H, J = 7.2, 2.4 Hz),7.88 (dd, 2H, J = 9, 1.8 Hz), 8.25 (d, 1H, J = 9 Hz), 8.59 (d, 1H, J =1.8 Hz), 9.35 (s, 1H). 262 688 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t,3H, J = 7.2 Hz), 1.26 (m, 6H), 1.40 (m, 2H), 1.75 (m, 4H), 1.85 (m, 2H),1.93 (m, 2H), 2.35 (m, 3H), 2.58 (s, 3H), 2.79 (m, 1H), 2.92 (m, 4H),3.22 (m, 2H), 3.42 (t, 2H, J = 11.4 Hz), 3.97 (t, 2H, J = 7.2 Hz), 6.95(d, 2H, J = 9 Hz), 7.23 (m, 1H), 7.33 (t, 2H, J = 7.8 Hz), 7.52 (d, 2H,J = 7.2 Hz), 7.63 (dd, 1H, J = 9, 1.8 Hz), 7.77 (m, 3H), 7.99 (d, 1H, J= 9 Hz), 9.11 (m, 1H) 263 704.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.86 (t,3H, J = 7.2 Hz), 1.24 (m, 6H), 1.41 (m, 2H), 1.77 (m, 4H), 1.85 (m, 2H),1.98 (m, 4H), 2.35 (m, 2H), 2.80 (s, 3H), 2.91 (m, 4H), 3.34 (m, 2H),3.51 (m, 2H), 3.99 (t, 2H, J = 6 Hz), 6.95 (d, 2H, J = 9 Hz), 7.23 (m,1H), 7.33 (t, 2H, J = 7.8 Hz), 7.52 (d, 2H, J = 7.2 Hz), 7.63 (dd, 1H, J= 9, 1.8 Hz), 7.77 (m, 3H), 7.99 (d, 1H, J = 9 Hz), 9.11 (m, 1H) 264669.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.83 (t, 3H, J = 7.8 Hz), 1.23 (m,12H), 1.36 (m, 4H), 1.72 (m, 4H), 1.84 (m, 2H), 2.53 (s, 3H), 2.61 (m,1H), 2.78 (s, 3H), 2.85 (m, 6H), 3.28 (m, 2H), 3.35 (m, 2H), 3.98 (t,2H, J = 6.6 Hz), 6.95 (d, 2H, J = 9 Hz), 7.72 (dd, 1H, J = 9, 1.8 Hz),7.78 (d, 2H, J = 9 Hz), 8.21 (d, 1H, J = 8.4 Hz), 8.59 (d, 1H, J = 1.2Hz), 9.33 (s, 1H). 265 670.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.87 (m,3H), 1.23 (m, 14H), 1.44 (m, 2H), 1.61 (m, 3H), 1.78 (m, 6H), 2.49 (m,1H), 2.67 (m, 4H), 2.80 (s, 3H), 3.33 (m, 4H), 4.00 (m, 2H), 6.97 (m,2H), 7.80 (m, 3H), 8.23 (m, 1H), 8.59 (m, 1H), 9.31 (m, 1H). 266 698¹HNMR (600 MHz, CDCl₃, 25° C.): 0.83 (t, 3H, J = 7.8 Hz), 1.23 (m, 22H),1.37 (m, 4H), 1.73 (m, 4H), 1.86 (m, 2H), 2.74 (s, 3H), 2.93 (m, 4H),3.43 (m, 4H), 3.94 (t, 2H, J = 6.6 Hz), 6.92 (d, 2H, J = 9 Hz), 7.63(dd, 1H, J = 8.4, 1.8 Hz), 7.80 (m, 2H), 8.00 (d, 1H, J = 8.4 Hz), 8.69(d, 1h, J = 1.8 Hz), 9.00 (s, 1H). 267 683.3 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.83 (t, 3H, J = 7.2 Hz), 1.24 (m, 14H), 1.44 (m, 2H), 1.75 (m,4H), 2.11 (m, 2H), 2.63 (s, 3H), 2.79 (m, 4H), 2.89 (m, 2H), 2.99 (m,4H), 3.07 (m, 2H), 3.28 (m, 2H), 3.43 (t, 2H, J = 10.8 Hz), 3.98 (t, 2H,J = 6.6 Hz), 6.95 (d, 2H, J = 9 Hz), 7.72 (dd, 1H, J = 8.4, 1.2 Hz),7.76 (d, 2H, J = 9 Hz), 8.20 (d, 1H, J = 8.4 Hz), 8.57 (d, 1H, J = 1.2Hz), 9.26 (s, 1H). 268 699 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H,J = 7.2 Hz), 1.21 (m, 12H), 1.40 (m, 2H), 1.71 (m, 4H), 1.86 (m, 2H),2.40 (m, 2H), 2.51 (m, 10H), 2.79 (s, 3H), 3.33 (m, 2H), 3.44 (m, 2H),3.63 (t, 2H, J = 5.4 Hz), 3.98 (t, 2H, J = 6.6 Hz), 6.96 (d, 2H, J = 9Hz), 7.77 (dd, 1H, J = 9, 1.8 Hz), 7.79 (d, 2H, J = 9 Hz), 8.20 (d, 1H,J = 9 Hz), 8.57 (d, 1H, J = 1.8 Hz), 9.26 (s, 1H). 269 734 ¹HNMR (600MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2 Hz), 1.24 (m, 12H), 1.42 (m,2H), 1.54 (m, 2H), 1.71 (m, 12H), 2.06 (m, 2H), 2.27 (m, 2H), 2.58 (m,1H), 2.67 (m, 1H), 2.79 (s, 3H), 2.81 (m, 4H), 3.09 (m, 2H), 3.30 (m,2H), 3.44 (t, 2H, J = 12 Hz), 3.98 (t, 2H, J = 6.6 Hz), 6.95 (m, 2H),7.74 (dd, 1H, J = 9, 2.4 Hz), 7.77 (m, 2H), 8.20 (d, 1H, J = 8.4 Hz),8.56 (d, 1H, J = 1.8 Hz), 9.26 (s, 1H). 270 747 1HNMR (600 MHz, CDCl3,25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.21 (m, 12H), 1.41 (m, 2H), 1.76 (m,2H), 1.92 (m, 4H), 2.10 (m, 3H), 2.57 (m, 2H), 2.80 (s, 3H), 3.15 (m,4H), 3.33 (m, 2H), 3.52 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 6.97 (m, 2H),7.22 (t, 1H, J = 7.2 Hz), 7.31 (t, 2H, J = 7.8 Hz), 7.53 (d, 2H, J = 7.2Hz), 7.77 (dd, 1H, J = 8.4, 1.8 Hz), 7.80 (d, 2H, J = 9 Hz), 8.22 (d,1H, J = 9 Hz), 8.55 (s, 1H), 9.24 (m, 1H). 272 611.2 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2 Hz), 1.22 (m, 8H), 1.40 (m, 2H),1.75 (m, 2H), 2.06 (m, 3H), 2.56 (m, 6H), 2.67 (m, 1H), 2.88 (m, 2H),3.10 (m, 2H), 3.25 (m, 7H), 3.96 (t, 2H, J = 12.6 Hz), 6.93 (d, 2H, J =9 Hz), 7.60 (dd, 1H, J = 9, 2.4 Hz), 7.74 (d, 2H, J = 9 Hz), 7.83 (d,1H, J = 1.8 Hz), 7.97 (d, 1H, J = 9 Hz), 9.14 (s, 1H). 273 639.3 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.85 (t, 2H, J = 7.2 Hz), 1.23 (d, 6H, J = 5.4Hz), 1.31 (m, 9H), 1.41 (m, 2H), 1.75 (m, 2H), 2.00 (m, 4H), 2.47 (m,3H), 2.57 (s, 3H), 2.59 (m, 3H), 3.00 (m, 1H), 3.19 (m, 2H), 3.30 (m,4H), 3.99 (t, 2H, J = 6.6 Hz), 6.94 (d, 2H, J = 9 Hz), 7.63 (dd, 1H, J =8.4, 1.8 Hz), 7.76 (dd, 2H, J = 7.1, 1.8 Hz), 7.89 (d, 1H, J = 1.8 Hz),8.01 (d, 1H, J = 9 Hz), 9.20 (s, 1H). 274 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.87 (t, 3H, J = 6.6 Hz), 1.24 (m, 6H), 1.42 (m, 2H), 1.75 (m, 3H),2.02 (m, 1H), 2.40 (m, 3H), 2.49 (m, 3H), 2.60 (s, 3H), 2.62 (m, 1H),2.73 (m, 1H), 2.78 (m, 1H), 2.97 (m, 1H), 3.29 (m, 4H), 3.95 (t, 2H, J =6.6 Hz), 6.90 (d, 2H, J = 9 Hz), 7.27 (m, 1H), 7.33 (m, 4H), 7.65 (dd,1H, J = 8.4, 1.8 Hz), 7.74 (d, 2H, J = 9 Hz), 7.94 (d, 1H, J = 1.8 Hz),8.04 (d, 1H, J = 9 Hz), 9.28 (s, 1H). 275 701.3 ¹HNMR (600 MHz, CDCl₃,25° C.): 0.88 (t, 3H, J = 7.2 Hz), 1.25 (m, 8H), 1.43 (m, 3H), 1.75 (m,4H), 1.95 (m, 2H), 2.24 (m, 2H), 2.28 (d, 2H, J = 6.2.45 (m, 4H), 2.58(s, 3H), 2.91 (m, 2H), 3.27 (m, 4H), 3.49 (m, 2H), 3.99 (t, 2H, J = 6.6Hz), 6.95 (d, 2H, J = 8.4 Hz), 7.25 (m, 1H), 7.31 (m, 4H), 7.64 (dd, 1H,J = 8.4, 1.8 Hz), 7.81 (d, 2H, J = 9 Hz), 7.93 (d, 1H, J = 1.8 Hz), 8.20(d, 1H, J = 9 Hz), 9.26 (s, 1H). 276 628.2 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.85 (t, 3H, J = 7.2 Hz), 1.28 (m, 8H), 1.40 (m, 2H), 1.75 (m, 2H),1.80 (m, 3H), 2.60 (m, 3H), 2.68 (m, 2H), 2.79 (m, 7H), 3.36 (m, 4H),3.62 (m, 2H), 3.97 (t, 2H, J = 12.6 Hz), 6.94 (d, 2H, J = 9 Hz), 7.79(dd, 2H, J = 7.2, 2.4 Hz), 7.85 (dd, 1H, J = 9, 1.8 Hz), 8.25 (d, 1H, J= 9 Hz), 8.62 (d, 1H, J = 1.8 Hz), 9.38 (s, 1H). 277 655.3 ¹HNMR (600MHz, CDCl₃, 25° C.): 0.87 (t, 2H, J = 7.2 Hz), 1.07 (d, 6H, J = 6 Hz),1.24 (m, 6H), 1.41 (m, 2H), 1.63 (m, 2H), 1.76 (m, 2H), 1.86 (m, 2H),2.19 (m, 3H), 2.36 (m, 1H), 2.64 (m, 4H), 2.79 (s, 3H), 3.00 (m, 2H),3.36 (m, 4H), 3.98 (t, 2H, J = 6.6 Hz), 6.94 (d, 2H, J = 9 Hz), 7.79 (d,2H, J = 9 Hz), 7.84 (dd, 1H, J = 9, 1.2 Hz), 8.26 (d, 1H, J = 9 Hz),8.63 (d, 1H, J = 1.8 Hz), 9.41 (s, 1H). 278 690.3 ¹HNMR (600 MHz, CDCl₃,25° C.): 0.87 (t, 3H, J = 6.6 Hz), 1.24 (m, 6H), 1.42 (m, 2H), 1.75 (m,3H), 2.04 (m, 2H), 2.43 (m, 3H), 2.57 (m, 3H), 2.80 (s, 3H), 2.87 (m,1H), 3.01 (m, 1H), 3.38 (m, 4H), 3.65 (m, 2H), 3.96 (t, 2H, J = 6.6 Hz),6.92 (d, 2H, J = 9 Hz), 7.27 (m, 1H), 7.32 (m, 4H), 7.77 (d, 2H, J = 7.2Hz), 8.27 (d, 1H, J = 9 Hz), 8.59 (s, 1H), 9.40 (s, 1H). 279 717.3 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.26 (m, 6H), 1.40(m, 2H), 1.53 (m, 3H), 1.76 (m, 2H), 1.84 (m, 2H), 2.23 (m, 2H), 2.28(d, 2H, J = 6.6 Hz), 2.52 (m, 4H), 2.79 (s, 3H), 3.11 (m, 2H), 3.37 (m,4H), 3.76 (m, 2H), 3.97 (t, 2H, J = 12.6 Hz), 6.95 (dd, 2H, J = 7.2, 1.8Hz), 7.30 (m, 3H), 7.41 (m, 2H), 7.79 (m, 3H), 8.21 (d, 1H, J = 9 Hz),8.62 (d, 1H, J = 1.8 Hz), 9.30 (s, 1H). 281 625.2 ¹HNMR (600 MHz, CDCl₃,25° C.): 0.87 (t, 3H, J6.6 Hz), 1.27 (m, 6H), 1.41 (m, 4H), 1.60 (m,4H), 1.77 (m, 2H), 2.46 (m, 9H), 2.58 (s, 3H), 2.60 (m, 2H), 3.82 (m,4H), 3.98 (t, 2H, J = 6.6 Hz), 6.94 (d, 2H, J = 9 Hz), 7.64 (dd, 1H, J =9, 1.8 Hz), 7.78 (d, 2H, J = 9 Hz), 7.92 (d, 1H, J = 1.8 Hz), 8.00 (d,1H, J = 9 Hz), 9.27 (s, 1H). 282 642.3 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.85 (t, 3H, J = 7.8 Hz), 1.28 (m, 6H), 1.42 (m, 2H), 1.51 (m, 2H), 1.74(m, 6H), 2.60 (m, 4H), 2.71 (m, 7H), 2.79 (s, 3H), 3.85 (m, 4H), 3.98(t, 2H, J = 6.6 Hz), 6.94 (d, 2H, J = 9 Hz), 7.78 (dd, 2H, J = 7.2, 1.8Hz), 7.83 (dd, 1H, J = 9, 1.8 Hz), 8.25 (d, 1H, J = 8.4 Hz), 8.61 (d,1H, J = 1.8 Hz), 9.37 (s, 1H). 283 697.3 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.83 (t, 3H, J = 7.2 Hz), 1.81 (m, 17H), 1.37 (m, 2H), 1.75 (m, 2H),1.97 (m, 4H), 2.47 (m, 4H), 2.67 (m, 4H), 2.80 (s, 3H), 3.06 (m, 1H),3.17 (m, 2H), 3.32 (m, 4H), 3.98 (t, 2H, J = 6.6 Hz), 6.95 (d, 2H, J = 9Hz), 7.78 (d, 2H, J = 9 Hz), 7.81 (dd, 1H, J = 8.4, 1.2 Hz), 8.25 (d,1H, J = 9 Hz), 8.63 (d, 1H, J = 1.8 Hz), 9.37 (s, 1H). 284 699.3 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.84 (d, 6H, J = 6.6 Hz), 0.91 (d, 3H, J = 6.6Hz), 1.11 (m, 3H), 1.22 (m, 4H), 1.48 (m, 1H), 1.56 (m, 1H), 1.61 (m,1H), 1.80 (m, 5H), 2.66 (m, 1H), 2.80 (s, 3H), 2.86 (m, 5H), 3.00 (m,4H), 3.29 (m, 2H), 3.39 (m, 2H), 3.79 (m, 2H), 4.02 (m, 2H), 6.97 (d,2H, J = 9 Hz), 7.72 (dd, 1H, J = 8.4, 1.8 Hz), 7.80 (d, 12H, J = 9 Hz),8.23 (d, 1H, J = 8.4 Hz), 8.61 (d, 1H, J = 1.2 Hz), 9.32 (s, 1H). 285752.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.24 (m,14H), 1.44 (m, 2H), 1.78 (m, 9H), 2.39 (s, 3H), 2.45 (m, 3H), 2.77 (m,8H), 2.80 (s, 3H), 3.15 (m, 2H), 3.20 (m, 2H), 3.49 (m, 2H), 3.99 (t,2H, J = 6.6 Hz), 6.97 (d, 2H, J = 9 Hz), 7.77 (dd, 1H, J = 9, 1.8 Hz),7.79 (d, 2H, J = 9 Hz), 8.21 (d, 1H, J = 9 Hz), 8.55 (d, 1H, J = 1.2Hz), 9.25 (s, 1H). 286 739.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84 (t,3H, J = 7.2 Hz), 1.24 (m, 12H), 1.40 (m, 2H), 1.75 (m, 10H), 2.31 (m,1H), 2.56 (m, 6H), 2.80 (s, 3H), 2.85 (m, 1H), 3.18 (m, 2H), 3.31 (m,2H), 3.48 (q, 2H, J = 9 Hz), 3.71 (t, 4H, J = 4.2 Hz), 3.96 (t, 2H, J =6 Hz), 6.97 (d, 2H, J = 9 Hz), 7.61 (dd, 1H, J = 9, 1.8 Hz), 7.79 (d,2H, J = 9 Hz), 8.20 (d, 1H, J = 8.4 Hz), 8.54 (d, 1H, J = 1.2 Hz), 9.23(s, 1H). 287 766 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2Hz), 1.17 (m, 14H), 1.43 (m, 2H), 1.52 (m, 2H), 1.66 (m, 2H), 1.76 (m,7H), 2.17 (m, 2H), 2.35 (s, 3H), 2.40 (m, 1H), 2.53 (m, 5H), 2.74 (m,6H), 3.01 (m, 2H), 3.25 (m, 2H), 3.45 (m, 2H), 3.97 (t, 2H, J = 6.6 Hz),6.94 (d, 2H, J = 9 Hz), 7.77 (m, 3H), 8.20 (d, 1H, J = 9 Hz), 8.55 (d,1H, J = 1.8 Hz), 9.26 (s, 1H). 288 753.3 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.85 (t, 3H, J = 7.2 Hz), 1.24 (m, 18H), 1.77 (m, 14H), 2.44 (m, 2H),2.67 (m, 2H), 2.81 (m, 7H), 3.06 (q, 1H, J = 14.4 Hz), 3.21 (m, 2H),3.32 (m, 2H), 3.47 (m, 2H), 3.99 (t, 3H, J = 6 Hz), 6.98 (d, 2H, J = 8.4Hz), 7.76 (dd, 1H, J = 9, 1.8 Hz), 7.79 (d, 2H, J = 9 Hz), 8.22 (d, 1H,J = 8.4 Hz), 8.56 (s, 1H), 9.25 (s, 1H). 289 737.3 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.83 (d, 6H, J = 6.6 Hz), 0.91 (d, 3H, J = 6 Hz), 1.13(m, 3H), 1.22 (m, 4H), 1.37 (m, 2H), 1.47 (m, 1H), 1.55 (m, 1H), 1.62(m, 1H), 1.80 (m, 1H), 1.96 (m, 4H), 2.07 (m, 4H), 2.41 (m, 4H), 2.81(s, 3H), 3.03 (m, 6H), 3.12 (m, 2H), 3.45 (m, 5H), 4.02 (m, 2H), 6.99(d, 2H, J = 9 Hz), 7.75 (d, 1H, J = 9 Hz), 7.78 (d, 2H, J = 9 Hz), 8.20(d, 1H, J = 9 Hz), 8.52 (s, 1H), 9.20 (m, 1H). 290 755.3 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.82 (m, 3H), 1.26 (m, 16H), 2.07 (m, 12H), 2.33 (m,4H), 2.50 (m, 2H), 2.80 (m, 5H), 3.24 (m, 6H), 3.48 (m, 2H), 4.08 (m,2H), 7.08 (m, 1H), 7.56 (m, 1H), 7.64 (m, 1H), 7.76 (m, 1H), 8.63 (m,1H), 8.57 (m, 1H (, 9.23 (m, 1H). 291 717.3 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.82 (t, 3H, J = 7.2 Hz), 1.22 (m, 12H), 1.40 (m, 2H), 1.77 (m,6H), 2.66 (m, 1H), 2.79 (s, 3H), 2.86 (m, 6H), 3.01 (m, 4H), 3.27 (m,2H), 3.36 (m, 2H), 3.78 (t, 2H, J = 4.8 Hz), 4.05 (t, 2H, J = 6.6 Hz),7.04 (t, 1H, J = 8.4 Hz), 7.55 (dd, 1H, J = 9.6, 1.8 Hz), 7.64 (d, 1H, J= 8.4 Hz), 7.73 (dd, 1H, J = 8.4, 1.2 Hz), 8.23 (d, 1H, J = 9 Hz), 8.60(s, 1H), 9.32 (s, 1H). 292 782.1 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84(t, 3H, J = 7.2 Hz), 1.23 (m, 16H), 1.40 (m, 2H), 1.76 (m, 6H), 1.93 (m,4H), 2.45 (m, 2H), 2.66 (m, 2H), 2.74 (m, 4H), 2.80 (s, 3H), 3.17 (m,2H), 3.31 (m, 2H), 3.46 (m, 2H), 3.68 (m, 3H), 3.98 (t, 2H, J = 6.6 Hz),6.97 (d, 2H, J = 9 Hz), 7.76 (dd, 1H, J = 8.4, 1.2 Hz), 7.79 (d, 2H, J =8.4 Hz), 8.21 (d, 1H, J = 9 Hz), 8.55 (s, 1H), 9.24 (s, 1H). 293 431(400 MHz, DMSO-d₆): 9.20 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.48 (s,1H), 7.16 (d, J = 8.8 Hz, 2H), 7.12 (s, 1H), 3.97 (s, 3H), 3.89 (s, 3H),3.83 (s, 3H), 3.27 (q, J = 7.2 Hz, 4H), 0.60 (t, J = 7.2 Hz, 6H) 294 445(400 MHz, DMSO-d₆): 9.23 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.47 (s,1H), 7.19 (s, 1H), 7.14 (d, J = 8.8 Hz, 2H), 3.97 (s, 3H), 3.89 (s, 3H),3.83 (s, 3H), 3.83-3, 75 (m, 1H), 3.21 (q, J = 8.Hz, 2H), 1.10-0.98 (brm, 6H) 1.12 (t, J = 7.2 Hz, 3H) 295 487.4 (400 MHz, DMSO-d₆): 9.19 (s,1H), 7.83 (d, J = 8.8 Hz, 2H), 7.46 (s, 1H), 7.18 (s, 1H), 7.14 (d, J =8.8 Hz, 2H), 3.96 (s, 3H), 3.88 (s, 3H), 3.82 (s, 3H), 3.19 (t, J = 7.2Hz, 4H), 1.02 (quint, J = 7.2 Hz, 4H), 1.02- 0.76 (m, 4H), 0.67 (t, J =7.2 Hz, 6H) 296 502 (400 MHz, DMSO-d₆): 9.17 (s, 1H), 7.84 (d, J = 8.8Hz, 2H), 7.46 (s, 1H), 7.30 (s, 1H), 7.14 (d, J = 8.8 Hz, 2H), 3.97 (s,3H), 3.89 (s, 3H), 3.83 (s, 3H), 3.29 (q, J = 7.2 Hz, 4H), 2.19 (q, J =7.2 Hz, 4H), 1.92 (br t, 2H), 0.74 (t, J = 7.2 Hz, 3H), 0.70 (t, J = 7.2Hz, 6H) 297 474 (400 MHz, DMSO-d₆): 8.70 (s, 1H), 7.90 (d, J = 8.8 Hz,2H), 7.57 (s, 1H), 7.53-7.50 (br t, 1H), 7.23 (s, 1H), 7.11 (d, J = 8.8Hz, 2H), 3.90 (s, 3H), 3.88 (s, 3H), 3.88-3.84 (m, 2H), 3.82 (s, 3H),2.67-2.60 (m, 6H), 1.03 (t, J = 7.2 Hz, 6H) 298 488 (400 MHz, DMSO-d₆):8.75 (s, 1H), 7.91 (d, J = 8.8 Hz, 2H), 7.41 (s, 1H), 7.26 (s, 1H), 7.12(d, J = 8.8 Hz, 2H), 6.83 (t, J = 6.8 Hz 1H), 3.92 (s, 3H), 3.87 (s,3H), 3.82 (s, 3H), 3.66 (q, J = 6.4 Hz 2H), 2.40-2.32 (m, 6H), 1.66-1.58(m, 2H), 0.86 (t, J = 7.2 Hz, 6H) 299 502 (400 MHz, DMSO-d₆): 8.74 (s,1H), 7.90 (d, J = 8.8 Hz, 2H), 7.43 (s, 1H), 7.26 (s, 1H), 7.12 (d, J =8.8 Hz, 2H), 6.87 (t, J = 5.2 Hz, 1H), 3.91 (s, 3H), 3.88 (s, 3H), 3.82(s, 3H), 3.72-3.66 (m, 2H), 2.38 (q, J = 7.2 Hz, 4H), 2.32-2.28 (m, 2H),1.55-1.47 (m, 2H), 1.41-1.33 (m, 2H), 0.88 (t, J = 7.2 Hz, 6H) 300 502.2(400 MHz, DMSO-d₆): 9.18 (s, 1H), 7.81 (d, J = 8.8 Hz, 2H), 7.50 (s,1H), 7.15 (d, J = 8.8 Hz, 2H), 7.12 (s, 1H), 3.97 (s, 3H), 3.90 (s, 3H),3.83 (s, 3H), 3.15-3.09 (m, 2H), 2.68 (s, 3H), 2.23 (q, J = 7.2 Hz, 4H),2.14-2.10 (m, 2H), 1.09-1.01 (m, 2H), 0.78 (t, J = 7.2 Hz, 6H) 301 488(400 MHz, DMSO-d₆): 9.13 (s, 1H), 7.79 (d, J = 8.8 Hz, 2H), 7.52 (s,1H), 7.36 (s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 4.45-4.40 (m, 1H), 3.98 (s,3H), 3.93 (s, 3H), 3.83 (s, 3H), 3.54-3.49 (m, 2H), 3.09 (br s, 4H),2.46- 2.41 (m, 2H), 2.37 (br s, 4H) 302 557.2 (400 MHz, CDCl₃): 9.29 (s,1H), 7.81 (d, J = 8.8 Hz, 2H), 7.48 (s, 1H), 7.41 (s, 1H), 6.97 (d, J =8.8 Hz, 2H), 4.06 (s, 3H), 4.01 (s, 3H), 3.87 (s, 3H), 3.25 (br s, 4H),2.65-2.48 (m, 6H), 2.48-2.38 (m, 6H), 1.70(br s, 2H), 1.11-1.03 (br t,6H) 303 459.4 (400 MHz, DMSO-d₆): 9.14 (s, 1H), 7.80 (d, J = 8.8 Hz,2H), 7.51 (s, 1H), 7.38 (br s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 4.71 (d, J= 4.0 Hz 1H), 3.98 (s, 3H), 3.92 (s, 3H), 3.83 (s, 3H), 3.74-3.66 (m,1H), 3.19-2.94 (br m, 4H), 1.68-1.59 (m, 2H), 1.44-1.34 (br m, 2H) 304473.4 (400 MHz, DMSO-d₆): 9.08 (br s, 1H), 7.79 (d, J = 8.8 Hz, 2H),7.48 (s, 1H), 7.33 (s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 4.42-4.35 (br m,1H), 3.97 (s, 3H), 3.93 (s, 3H), 3.83 (s, 3H), 3.29-3.18 (m, 2H),3.17-3.10 (m, 1H), 3.09-2.98 (br m, 1H), 2.91 (m, 1H), 2.85-2.77 (br m,1H), 1.79-1.39 (br m, 3H), 1.14-1.05 (m, 1H) 305 445 (400 MHz, DMSO-d₆):9.21 (s, 1H), 7.89 (s, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.53 (s, 1H), 7.11(d, J = 8.8 Hz, 2H), 5.37 (d, J = 2.0 Hz, 1H), 4.40 (br s, 1H), 3.97 (s,3H), 3.84 (s, 3H), 3.82 (s, 3H), 3.02 (m, 1H), 2.91- 2.85 (m, 1H),1.95-1.87 (br m, 2H) 306 470.2 (400 MHz, DMSO-d₆): 9.17 (s, 1H), 8.44(s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.45 (s, 1H), 7.08 (d, J = 8.8 Hz,2H), 4.37 (s, 1H), 3.96 (s, 3H), 3.89 (s, 3H), 3.79 (s, 3H), 3.55 (d, J= 7.2 Hz, 1H), 3.01 (d, J = 9.6 Hz, 1H), 2.39 (s, 1H), 2.25 (d, J = 9.6Hz, 1H), 2.01 (d, J = 8.8 Hz, 1H), 1.85 (q, J = 8.0 Hz, 2H) 307 543 (400MHz, DMSO-d₆): 9.14 (s, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.62 (br s, 1H),7.49 (s, 1H), 7.14 (d, J = 8.8 Hz, 2H), 3.97 (s, 3H), 3.93 (s, 3H), 3.83(s, 3H), 3.41 (br s, 2H), 3.22-3.13 (m, 2H), 2.99 (s, 3H), 2.99-2.90 (brm, 2H), 2.84-2.76 (br m, 2H), 2.81 (s, 3H), 2.74-2.65 (m, 2H), 1.79-1.70 (br s, 2H) 308 535 (400 MHz, DMSO-d₆): 9.23 (s, 1H), 7.89 (d, J =8.8 Hz, 2H), 7.63 (br s, 1H), 7.56 (s, 1H), 7.52 (d, J = 8.0 Hz, 2H),7.40 (t, J = 7.6 Hz, 2H), 7.26 (t, J = 8.0 Hz, 1H), 7.15 (d, J = 8.8 Hz,2H), 5.23 (s, 1H), 4.00 (s, 3H), 3.94 (s, 3H), 3.84-3.76 (br m, 2H),3.80 (s, 3H), 2.58-2.48 (br m, 2H), 1.83-1.70 (m, 2H), 1.55-1.46 (br d,2H) 309 577 (400 MHz, DMSO-d₆): 9.19 (br s, 1H), 7.97 (d, J = 8.0 Hz,2H), 7.83 (d, J = 8.8 Hz, 2H), 7.55 (s, 1H), 7.41 (d, J = 8.0 Hz, 2H),7.38 (s, 1H), 7.17 (d, J = 8.8 Hz, 2H), 4.00 (s, 3H), 3.98 (s, 3H), 3.86(s, 3H), 3.80 (s, 3H), 3.50 (m, 2H), 2.97-2.79 (m, 4H), 1.63-1.55 (m,2H), 1.49-1.35 (br m, 1H) 310 576 (400 MHz, DMSO-d₆): 9.18 (br s, 1H),8.41-8.36 (br m, 1H), 7.83 (t, J = 7.6 Hz, 4H), 7.55 (s, 1H), 7.38 (s,1H), 7.33 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 4.00 (s, 3H),3.98 (s, 3H), 3.81 (s, 3H), 3.54-3.42 (m, 2H), 3.00-2.85 (m, 2H),2.85-2.74 (m, 2H), 2.79 (d, J = 4.4 Hz, 3H), 1.63-1.54 (br m, 1H) 311549 (400 MHz, DMSO-d₆): 9.17 (br s, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.54(s, 1H), 7.38 (s, 1H), 7.20-7.12 (m, 4H), 6.92 (d, J = 8.8 Hz, 2H), 3.99(s, 3H), 3.97 (s, 3H), 3.81 (s, 3H), 3.75 (s, 3H), 3.47 (m, 2H),2.96-2.86 (m, 2H), 2.70-2.62 (m, 1H), 1.59-1.50 (br m, 2H), 1.45-1.33(br m, 1H) 312 602.2 (400 MHz, CDCl₃): 9.32-9.20 (br s, 1H), 7.86 (d, J= 8.8 Hz, 2H), 7.51- 7.34 (br m, 4H), 7.23 (d, J = 8.0 Hz, 2H), 6.99 (d,J = 8.8 Hz, 2H), 4.07 (s, 3H), 4.05 (s, 3H), 3.86 (s, 3H), 3.83-3.69 (brs, 1H), 3.57-3.47 (m, 4H), 3.21-3.11 (m, 2H), 2.79-2.57 (m, 3H),1.99-1.49 (br m, 9H) 313 505.4 (400 MHz, DMSO-d₆): 9.23 (s, 1H), 7.86(d, J = 8.8 Hz, 2H), 7.57 (s, 1H), 7.38-7.30 (m, 4H), 7.27-7.22 (m, 1H),7.15 (d, J = 8.8 Hz, 2H), 7.06 (s, 1H), 3.99 (s, 3H), 3.95 (s, 3H), 3.80(s, 3H), 3.68-3.59 (m, 1H), 3.30- 3.16 (m, 3H), 2.76 (t, J = 9.6 Hz,1H), 2.40-2.32 (m, 1H), 2.26-2.19 (m, 1H) 314 549 (400 MHz, DMSO-d₆):9.22 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.56 (s, 1H), 7.15 (d, J = 8.0Hz, 2H), 7.04 (s, 1H), 6.89 (s, 1H), 6.87 (d, J = 8.8 Hz, 1H), 6.78 (d,J = 8.0 Hz, 1H), 5.99 (s, 2H), 3.98 (s, 3H), 3.94 (s, 3H), 3.81 (s, 3H),3.62-3.51 (br m, 1H), 3.27-3.14 (m, 3H), 2.73-2.66 (m, 1H), 2.35-2.28(m, 1H), 2.21-2.13 (m, 1H) 315 520.6 (400 MHz, DMSO-d₆): 9.18 (s, 1H),7.82 (d, J = 8.8 Hz, 2H), 7.54 (s, 1H), 7.27-7.20 (m, 3H), 7.11 (d, J =8.0 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 6.79 (t, J = 8.0 Hz, 1H), 3.98(s, 3H), 3.82 (s, 3H), 3.76 (s, 3H), 3.18 (br s, 8H) 316 551 (400 MHz,DMSO-d₆): 9.17 (s, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.54 (s, 1H), 7.32 (s,1H), 7.11 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 9.2 Hz, 2H), 6.84 (d, J =9.2 Hz, 2H), 3.99 (s, 3H), 3.84 (s, 3H), 3.82 (s, 3H), 3.70 (s, 3H),3.28-3.15 (br s, 4H), 3.08-2.95 (br s, 4H) 317 592 (400 MHz, DMSO-d₆):9.18 (s, 1H), 7.84-7.79 (m, 4H), 7.54 (s, 1H), 7.21 (s, 1H), 7.11 (d, J= 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 9.2 Hz, 2H), 4.26(q, J = 7.2 Hz, 2H), 3.98 (s, 3H), 3.82 (s, 3H), 3.74 (s, 3H), 3.38-3.07(br s, 8H), 1.30 (t, J = 7.2 Hz, 4H) 318 564.2 (400 MHz, DMSO-d₆): 9.25(s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.58 (s, 1H), 7.35 (d, J = 9.2 Hz,2H), 7.23 (s, 1H), 7.08 (d, J = 9.2 Hz, 2H), 7.03 (d, J = 9.2 Hz, 2H),4.00 (s, 3H), 3.94 (s, 3H), 3.80 (s, 3H), 3.78 (s, 3H), 3.60-3.54 (br s,2H) 319 645 (400 MHz, DMSO-d₆): 9.18 (s, 1H), 7.91 (d, J = 8.8 Hz, 1H),7.81 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H), 7.54 (s, 1H), 7.22(s, 1H), 7.10 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 3.98 (s,3H), 3.82 (s, 3H), 3.79- 3.69 (br s, 1H), 3.73 (s, 3H), 3.45-3.07 (br m,8H), 1.83-1.70 (br d, 4H), 1.65-1.58 (br d, 1H), 1.36-1.23 (m, 4H),1.19-1.07 (br m, 1 H) 320 526 (400 MHz, DMSO-d₆): 9.15 (s, 1H), 7.76 (d,J = 8.8 Hz, 2H), 7.52 (s, 1H), 7.31 (s, 1H), 7.11 (d, J = 8.8 Hz, 2H),3.98 (s, 3H), 3.94 (s, 3H), 3.83 (s, 3H), 3.28-3.19 (br m, 2H),2.99-2.87 (br m, 2H), 2.47-2.39 (br s, 4H), 1.56-1.23 (br m, 8H) 321526.5 (400 MHz, DMSO-d₆): 9.18 (s, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.54(s, 1H), 7.32 (s, 1H), 7.14 (d, J = 8.8 Hz, 2H), 3.99 (s, 3H), 3.98 (s,3H), 3.83 (s, 3H), 3.51-3.41 (br t, 2H), 2.89-2.80 (br d, 2H), 2.44 (t,J = 7.2 Hz, 2H), 2.01-1.92 (m, 2H), 1.45-1.30 (br m, 4H) 322 542 (400MHz, DMSO-d₆): 9.17 (s, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.53 (s, 1H),7.32 (s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 4.42-4.34 (br s, 1H), 3.98 (s,3H), 3.93 (s, 3H), 3.83 (s, 3H) 3.33-3.13 (br m, 4H), 3.06 (t, J = 7.2Hz, 1H), 3.02-2.87 (br m, 2H), 2.87-2.78 (br m, 2H), 2.68-2.58 (br m,1H), 1.73-1.52 (br m, 5H), 1.37-1.21 (br m, 1H) 323 502 (400 MHz,DMSO-d₆): 9.14 (s, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.54 (s, 1H), 7.50 (s,1H), 7.14 (d, J = 8.8 Hz, 2H), 3.97 (s, 3H), 3.93 (s, 3H), 3.83 (s, 3H)3.52 (t, J = 6.0 Hz, 2H), 2.79-2.73 (br m, 2H), 3.19-2.93 (br m, 4H),2.72-2.66 (br m, 2H), 2.64 (t, J = 6.0 Hz, 2H), 1.79-1.72 (br m, 2H) 324570 (400 MHz, TFA-d₁): Mixture of Diastereomers 8.29, 8.22, 8.16, 7.97(four s, 1H), 7.70-7.61 (m, 2H), 7.29-7.14 (br m, 2H), 6.99-6.89 (d,2H), 4.31-3.15 (br m, 22H) 3.13-2.71 (br m, 3H), 2.40-1.86 (m, 2H),1.05-0.78 (br m, 6H) 325 556 (400 MHz, DMSO-d₆): 9.14 (s, 1H), 7.82 (d,J = 8.8 Hz, 2H), 7.51 (s, 1H), 7.34 (s, 1H), 7.14 (d, J = 8.8 Hz, 2H),4.01 (s, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 3.83 (s, 3H), 3.21-3.13 (br m,2H), 3.09-2.98 (br m, 2H), 2.89-2.76 (br d, 4H), 2.60-2.50 (br m, 2H),1.81-1.63 (br m, 2H), 1.60- 1.43 (br m, 4H) 326 514 (400 MHz, DMSO-d₆):9.15 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.70 (s, 1H), 7.49 (s, 1H), 7.14(d, J = 8.8 Hz, 2H), 4.56 (t, J = 6.0 Hz, 2H), 4.39 (t, J = 6.0 Hz, 2H),3.98 (s, 6H), 3.83 (s, 3H), 3.63 (quint, J = 6.0 Hz, 1H), 3.30-3.24 (brm, 2H), 3.08-2.76 (br m, 1H), 2.48-2.38 (br m, 3H), 1.78- 1.69 (br m,2H) 327 626 (400 MHz, DMSO-d₆): 9.08 (s, 1H), 7.93 (d, J = 2.4 Hz, 1H),7.76 (d, J = 8.8 Hz, 2H), 7.51 (s, 1H), 7.45 (d, J = 8.8 Hz, 1H), 7.31(dd, ³J = 8.8 Hz, 1H), 7.19 (s, 1H), 6.99 (d, J = 8.8 Hz, 2H), 3.96 (s,3H), 3.91-3.83 (br s, 2H), 3.79 (s, 3H), 3.70-3.53 (br m, 2H), 3.63 (s,3H), 1.88-1.68 (br m, 2H) 328 486 (400 MHz, DMSO-d₆): 9.12 (s, 1H), 7.81(d, J = 8.8 Hz, 2H), 7.53 (s, 1H), 7.20 (s, 1H), 7.14 (d, J = 8.8 Hz,2H), 3.99 (s, 3H), 3.93 (s, 3H), 3.84 (s, 3H), 3.41-3.34 (br m, 2H),3.28-3.00 (br m, 2H), 2.90 (s, 3H), 2.45-2.37 (br s, 1H) 329 558 (400MHz, CDCl₃): 9.22 (s, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.54 (s, 1H), 7.45(s, 1H), 6.98 (d, J = 8.8 Hz, 2H), 4.05 (s, 3H), 4.01 (s, 3H), 3.88 (s,3H), 3.34-3.26 (br m, 2H), 3.22-3.11 (br m, 2H), 2.88-2.65 (br m, 8H),2.54-2.44 (br m, 1H), 1.87-1.78 (br m, 2H), 1.77-1.65 (br m, 2H) 330 590(400 MHz, CDCl₃): 9.11 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.46 (s, 1H),7.40 (s, 1H), 6.99 (d, J = 8.8 Hz, 2H), 4.06 (s, 3H), 4.01 (s, 3H), 3.88(s, 3H), 3.37-3.25 (br m, 3H), 3.21-3.12 (br m, 2H), 3.07-2.97 (br m,2H), 2.89-2.76 (br m, 4H), 2.30-2.14 (br m, 3H), 1.90-1.81 (br m, 2H)331 537 (400 MHz, DMSO-d₆): 9.38 (s, 1H), 8.25 (s, 1H), 8.20 (d, J = 8.0Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.13 (d, J= 8.8 Hz, 2H), 3.84 (s, 3H), 3.22-3.16 (br m, 2H), 3.09-3.01 (br m, 5H),2.94 (s, 3H), 2.50-2.40 (br s, 5H), 1.62-1.48 (br m, 5H), 1.44-1.33 (brm, 3H) 332 537 (400 MHz, CDCl₃): 9.27 (br s, 1H), 8.34 (br m, 1H), 8.21(s, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.02 (d, J= 8.8 Hz, 2H), 4.28-4.20 (br m, 1H), 3.69 (s, 3H), 3.68-3.58 (br t, 2H),3.44 (t, J = 8.0 Hz, 2H), 3.39-3.27 (br m, 1H), 3.21 (s, 3H), 3.05 (s,3H), 2.45 (t, J = 8.0 Hz, 2H), 2.09 (quint, J = 8.0 Hz, 2H), 1.88-1.59(br m, 5H) 333 554 (400 MHz, CDCl₃): 9.35-8.70 (br s, 1H), 8.21 (d, J =8.8 Hz, 2H), 7.98- 7.86 (m, 3H), 7.08 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H),3.64-3.31 (br m, 4H), 3.21 (s, 3H), 3.12-2.98 (m, 9H), 1.64-1.49 (br s,8H) 334 523 (400 MHz, CDCl₃): 9.22-9.13 (br s, 1H), 8.70 (s, 1H),8.18-8.10 (br d, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz,2H), 3.89 (s, 3H), 3.58- 3.46 (br m, 2H), 3.45-3.33 (br m, 2H), 3.12 (d,J = 4.0 Hz, 3H), 2.82- 2.55 (br m, 3H), 2.05-1.40 (br s, 12H) 335 469(400 MHz, CDCl₃): 9.27 (br s, 1H), 8.42 (d, J = 8.0 Hz, 1H), 8.18 (d, J= 8.0 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.44-7.31 (br s, 1H), 7.02 (d,J = 8.8 Hz, 2H), 3.89 (s, 3H), 3.70-3.60 (br m, 2H), 3.40-3.22 (br m,2H), 3.10 (d, J = 4.0 Hz, 3H), 2.99-2.82 (br m, 4H), 2.65 (s, 3H),2.01-1.89 (br m, 2H) 336 539 (400 MHz, CDCl₃): 9.31-9.04 (br s, 1H),8.68 (s, 1H), 8.28-8.07 (br s, 1H), 8.16 (d, J = 8.0 Hz, 1H), 7.85 (d, J= 8.8 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H), 3.77-3.24 (br m,6H), 3.11 (d, J = 4.0 Hz, 3H), 2.15- 1.78 (br m, 4H), 1.69-1.52 (br m,5H) 337 609 (400 MHz, CDCl₃): 9.32 (br s, 1H), 8.77 (s, 1H), 8.26-8.15(br m, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.88 (s,3H), 3.80-3.52 (br m, 4H), 3.33-3.24 (br m, 2H), 3.07-2.63 (br m, 5H),2.10-1.49 (br m, 13H), 1.37-1.11 (br m, 6H) 338 652.2 Mixture ofDiastereomers in CDCl₃ 9.48, 9.05 (two s, 1H), 8.80, 8.72 (two s, 1H),8.23-8.12 (br m, d, J = 8.0 Hz, 2H), 7.86, 7.80 (two d, J = 8.8 Hz, 2H),7.02, 6.99 (two, d, J = 8.8 Hz, 2H), 4.05-3.98 (m, 1H) 3.90, 3.88 (twos, 3H), 3.85-3.77 (m, 2H), 3.74-3.60 (m, 3H), 3.56-3.26 (m, 3H),3.17-3.06 (m, 1H), 3.04-2.65 (br m, 8H), 2.63-2.28 (br m, 2H), 1.95-1.50(br m, 5H), 1.32-1.08 (br m, 6H), 0.99-0.84 (br m, 6H) 339 727.4 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2 Hz), 1.22 (m, 16H), 1.40(m, 2H), 1.75 (m, 2H), 1.85 (m, 4H), 2.73 (m, 1H), 2.80 (s, 3H), 3.01(m, 6H), 3.21 (m, 6H), 3.42 (m, 2H), 3.90 (m, 2H), 3.99 (t, 2H, J = 6.6Hz), 6.97 (d, 2H, J = 8.4 Hz), 7.70 (dd, 1H, J = 9, 1.2 Hz), 7.80 (d,2H, J = 9 Hz), 8.24 (d, 1H, J = 8.4 Hz), 8.63 (s, 1H), 9.37 (s, 1H). 340810.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 6.6 Hz), 1.24 (m,18H), 1.42 (m, 2H), 1.76 (m, 6H), 1.91 (m, 4H), 2.41 (m, 3H), 2.65 (m,2H), 2.73 (m, 7H), 2.80 (s, 3H), 3.15 (m, 2H), 3.31 (m, 2H), 3.49 (m,2H), 3.67 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 6.97 (d, 2H, J = 9 Hz),7.77 (dd, 1H, J = 8.4, 1.2 Hz), 7.79 (d, 2H, J = 9 Hz), 7.21 (d, 1H, J =8.4 Hz), 8.55 (s, 1H), 9.24 (s, 1H). 341 780.5 ¹HNMR (600 MHz, CDCl₃,25° C.): 0.84 (t, 3H, J = 7.2 Hz), 1.23 (m, 18H), 1.40 (m, 2H), 1.79 (m,6H), 1.89 (m, 2H), 1.97 (m, 2H), 2.37 (m, 6H), 2.65 (m, 7H), 2.79 (s,3H), 3.12 (m, 2H), 3.30 (m, 2H), 3.45 (m, 2H), 3.98 (t, 2H, J = 6.6 Hz),6.96 (d, 2H, J = 9 Hz), 7.66 (dd, 1H, J = 9, 1.8 Hz), 7.78 (d, 2H, J = 9Hz), 8.20 (d, 1H, J = 8.4 Hz), 8.54 (d, 1H, J = 1.2 Hz), 9.25 (s, 1H).342 765.3 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.83 (t, 3H, J = 7.2 Hz), 1.23(m, 18H), 1.40 (m, 2H), 1.75 (m, 3H), 1.90 (m, 9H), 2.39 (m, 3H), 2.80(m, 3H), 2.82 (m, 4H), 3.29 (m, 6H), 3.48 (m, 3H), 3.98 (t, 2H, J = 6.6Hz), 6.98 (d, 2H, J = 8.4 Hz), 7.76 (m, 3H), 8.21 (d, 1H, J = 8.4 Hz),8.52 (s, 1H), 9.23 (s, 1H) 343 781.5 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.85 (t, 3H, J = 7.2 Hz), 1.25 (m, 18H), 1.41 (m, 2H), 1.66 (m, 3H),1.79 (m, 8H), 2.01 (m, 3H), 2.41 (m, 2H), 2.64 (m, 2H), 2.81 (s, 6H),3.19 (m, 2H), 3.33 (m, 2H), 3.47 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 6.97(d, 2H, J = 8.4 Hz), 7.67 (dd, 1H, J = 9, 1.8 Hz), 7.80 (d, 2H, J = 9Hz), 8.22 (d, 1H, J = 9 Hz), 8.56 (s, 1H), 9.25 (s, 1H). 344 755.3 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2 Hz), 1.24 (m, 22H), 1.40(m, 2H), 1.75 (m, 2H), 1.85 (m, 3H), 2.80 (s, 3H), 3.05 (m, 9H), 3.46(m, 6H), 3.96 (m, 1H), 4.02 (t, 2H, J = 6.6 Hz), 6.98 (d, 2H, J = 9 Hz),7.69 (d, 1H, J = 6.6 Hz), 7.81 (d, 2H, J = 8.4 Hz), 8.25 (d, 1H, J = 9Hz), 8.65 (s, 1H), 9.42 (s, 1H). 345 838.5 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.85 (t, 3H, J = 7.2 Hz), 1.21 (m, 24H), 1.45 (m, 2H), 1.77 (m,2H), 1.90 (m, 8H), 2.52 (m, 3H), 2.87 (m, 10H), 3.23 (m, 2H), 3.33 (m,2H), 3.49 (m, 2H), 3.70 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 6.94 (d, 2H,J = 9 Hz), 7.79 (d, 2H, J = 9 Hz), 7.84 (dd, 1H, J = 9, 1.2 Hz), 8.26(d, 1H, J = 9 Hz), 8.63 (d, 1H, J = 1.8 Hz), 9.41 (s, 1H). 346 808.3¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 6.6 Hz), 1.22 (m, 24H),1.77 (m, 2H), 1.98 (m, 2H), 2.10 (m, 6H), 2.56 (s, 3H), 2.60 (m, 3H),2.82 (s, 3H), 3.07 (m, 7H), 3.33 (m, 4H), 3.51 (m, 2H), 4.00 (t, 2H, J =6.6 Hz), 7.00 (d, 2H, J = 9 Hz), 7.77 (dd, 1H, J = 8.4, 1.2 Hz), 7.80(d, 2H, J = 9 Hz), 8.23 (d, 1H, J = 8.4 Hz), 8.53 (s, 1H), 9.23 (s, 1H).347 808.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.83 (t, 3H, J = 7.2 Hz), 1.22(m, 22H), 1.40 (m, 2H), 1.75 (m, 8H), 2.20 (m, 5H), 2.39 (m, 3H), 2.48(m, 2H), 2.80 (m, 4H), 3.21 (m, 7H), 3.43 (m, 2H), 3.98 (t, 2H, J = 6.6Hz), 6.96 (d, 2H, J = 9 Hz), 7.74 (dd, 1H, J = 9, 1.8 Hz), 7.77 (d, 2H,J = 9 Hz), 8.20 (d, 1H, J = 9 Hz), 8.54 (d, 1H, J = 1.2 Hz), 9.25 (s,1H) 348 809.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2 Hz),1.23 (m, 23H), 1.43 (m, 2H), 1.65 (m, 1H), 1.75 (m, 2H), 1.84 (m, 3H),1.95 (m, 2H), 2.13 (m, 5H), 2.64 (m, 2H), 2.81 (s, 3H), 2.93 (m, 4H),3.33 (m, 4H), 3.49 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 4.14 (m, 1H), 6.98(d, 2H, J = 9 Hz), 7.66 (dd, 1H, J = 9, 1.2 Hz), 7.79 (d, 2H, J = 9 Hz),8.21 (d, 1H, J = 9 Hz), 8.54 (s, 1H), 9.23 (s, 1H). 349 483.2 (400 MHz,CDCl₃): 9.36-9.18 (br s, 1H), 8.50-8.32 (br m, 1H), 8.18 (d, J = 8.4 Hz,1H), 7.92-7.83 (m, 3H), 7.04 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H),3.60-3.28 (br m, 4H), 3.24-2.95 (br m, 1H), 3.19 (s, 3H), 3.04 (s, 3H),2.94-2.41 (br m, 5H), 2.11-1.86 (br m, 1H), 1.77-1.52 (br m, 2H) 350 554(400 MHz, CDCl₃): 9.19 (s, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.85-7.75 (m,3H), 7.69 (d, J = 8.8 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 4.25-4.14 (m,1H), 4.02 (t, J = 6.4 Hz, 2H), 3.57 (t, J = 10.8 Hz, 2H), 3.44 (t, J =7.2 Hz, 2H), 3.25-3.12 (br m, 2H), 2.62 (s, 3H), 2.45 (t, J = 8.0 Hz,2H), 2.09 (quint, J = 8.0 Hz, 2H), 1.85-1.56 (br m, 7H), 1.50 (sextet, J= 8.0 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H) 351 571.2 (400 MHz, DMSO-d₆):9.23 (s, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.85-7.78 (m, 4H), 7.12 (d, J =8.8 Hz, 2H), 4.43-4.38 (m, 1H), 4.06 (t, J = 6.4 Hz, 2H), 3.31-3.17 (brm, 3H), 3.11-2.97 (br m, 3H), 2.63 (s, 3H), 1.75-1.57 (br m, 6H),1.47-1.27 (br m, 3H), 0.92 (t, J = 7.4 Hz, 3H) 352 530.2 (400 MHz,DMSO-d₆): 9.23 (s, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.95 (s, 1H), 7.85 (d,J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 1H), 7.14 (d, J = 8.8 Hz, 2H),4.45-4.40 (m, 1H), 4.06 (t, J = 6.4 Hz, 2H), 3.57-3.50 (m, 2H),3.22-3.15 (br s, 2H), 3.10-3.02 (br s, 2H), 2.77-2.65 (br m, 4H), 2.64-2.58 (br m, 5H), 1.78-1.65 (br m, 4H), 1.46-1.36 (m, 2H), 0.92 (t, J =7.4 Hz, 3H) 353 598.4 (400 MHz, DMSO-d₆): 9.24 (s, 1H), 8.06 (d, J = 8.8Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.75 (d, J = 8.8 Hz, 2H), 7.73 (s,1H), 7.09 (d, J = 8.8 Hz, 2H), 4.06 (t, J = 6.4 Hz, 2H), 3.75-3.67 (brm, 1H), 3.58-3.51 (br m, 1H), 3.47-3.40 (br m, 1H), 3.32-3.20 (br m,4H), 3.08-2.73 (br m, 5H), 2.63 (s, 3H), 2.23-2.13 (m, 2H), 1.75-1.51(br m, 3H), 1.50-1.37 (br m, 2H), 0.92 (t, J = 7.4 Hz, 6H), 0.86 (d, J =7.4 Hz, 3H) 354 647.2 (400 MHz, DMSO-d₆): 9.17 (s, 1H), 8.09 (t, J = 8.8Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.87-7.80 (m, 3H), 7.71 (s, 1H), 7.13(d, J = 8.8 Hz, 2H), 4.07 (t, J = 6.4 Hz, 2H), 3.80-3.69 (m, 2H),3.46-3.36 (m, 5H), 2.62 (s, 3H), 1.79-1.65 (br m, 4H), 1.47-1.37 (m,2H), 0.92 (t, J = 7.4 Hz, 3H) 355 586.4 (400 MHz, DMSO-d₆): 9.23 (s,1H), 8.05 (d, J = 8.8 Hz, 1H), 7.86-7.79 (m, 4H), 7.13 (d, J = 8.8 Hz,2H), 4.06 (t, J = 6.4 Hz, 2H), 3.24-3.17 (br s, 2H), 3.13-3.06 (br s,2H), 2.90-2.77 (br m, 4H), 2.63 (s, 3H), 2.57 (s, 2H), 1.80-1.65 (br m,6H), 1.62-1.36 (br m, 8H), 0.92 (t, J = 7.4 Hz, 3H) 356 542.2 (400 MHz,DMSO-d₆): 9.23 (s, 1H), 8.05-8.01 (m, 2H), 7.86 (d, J = 8.8 Hz, 2H),7.80 (d, J = 8.0 Hz, 1H), 7.14 (d, J = 8.8 Hz, 2H), 4.56 (t, J = 6.4 Hz,2H), 4.43 (t, J = 6.4 Hz, 2H), 4.06 (t, J = 6.4 Hz, 2H), 3.72-3.63 (m,1H), 3.13-3.06 (br s, 2H), 3.30-3.24 (br s, 2H), 3.06-2.96 (br s, 2H),2.65 (s, 3H), 2.49-2.39 (br m, 2H), 1.80-1.65 (br m, 4H), 1.41 (sextet,J = 7.4 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H) 357 654 (400 MHz, DMSO-d₆):9.18 (s, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 2.4 Hz, 1H),7.81-7.76 (m, 3H), 7.64 (s, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.31 (dd, ³J= 8.0 Hz, ⁴J = 2.4 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 3.98 (t, J = 6.4Hz, 2H), 3.90-3.33 (br m, 2H), 3.68-3.60 (br m, 2H), 2.36 (s, 3H),1.86-1.78 (br m, 2H), 1.73-1.65 (m, 2H), 1.41 (sextet, J = 7.4 Hz, 2H),0.93 (t, J = 7.4 Hz, 3H) 358 514 (400 MHz, CDCl₃): 9.05 (s, 1H),8.27-8.20 (br m, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.72 (d, J = 8.0 Hz,1H), 7.68 (s, 1H), 7.02 (d, J = 8.8 Hz, 2H), 4.04 (t, J = 6.4 Hz, 2H),3.67-3.36 (br m, 6H), 3.09 (s, 3H), 2.70-2.62 (br m, 2H), 2.60 (s, 3H),1.81 (quint, J = 8.0 Hz, 2H), 1.67-1.46 (br m, 4H), 1.00 (t, J = 7.4 Hz,3H) 359 587 (400 MHz, DMSO-d₆): 9.21(s, 1H), 8.09 (s, 1H), 8.03 (d, J =8.8 Hz, 1H), 7.89-7.79 (m, 3H), 7.14 (d, J = 8.8 Hz, 2H), 4.07 (t, J =6.4 Hz, 2H), 3.29-3.17 (br m, 4H), 3.12-2.87 (br m, 5H), 2.77-2.71 (brm, 2H), 2.68- 2.59 (br m, 5H), 2.11-2.03 (br m, 2H), 1.99-1.86 (m, 2H),1.74-1.65 (m, 4H), 1.42 (sxt, J = 7.4 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H)360 618 (400 MHz, DMSO-d₆): 9.22(s, 1H), 8.06-8.01 (m, 2H), 7.87-7.79(m, 3H), 7.14 (d, J = 8.8 Hz, 2H), 4.06 (t, J = 6.4 Hz, 2H), 3.28-3.17(br m, 4H), 3.12-2.88 (br m, 5H), 2.77-2.71 (m, 2H), 2.68-2.59 (br m,5H), 2.11-2.04 (br m, 2H), 1.99-1.86 (m, 2H), 1.74-1.65 (m, 4H), 1.42(sxt, J = 7.4 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H) 361 386.2 (400 MHz,CDCl₃): 8.95 (s, 1H), 8.93 (s, 1H), 8.00-7.90 (m, 3H), 7.84 (d, J = 8.8Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.52 (br s, 1H), 3.85 (s, 3H), 3.56(d, J = 5.2 Hz, 3H), 3.07 (d, J = 4.8 Hz, 3H) 362 745.4 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.82 (t, 3H, J = 7.2 Hz), 1.22 (m, 16H), 1.40 (m, 2H),1.79 (m, 6H), 2.67 (m, 1H), 2.79 (s, 3H), 2.92 (m, 6H), 3.11 (m, 4H),3.23 (m, 2H), 3.38 (m, 2H), 3.82 (m, 2H), 4.05 (t, 2H, J = 6.6 Hz), 7.04(t, 1H, J = 7.8 Hz), 7.54 (dd, 1H, J = 10.2, 2.4 Hz), 7.64 (dd, 1H, J =9, 1.8 Hz), 7.72 (dd, 1H, J = 9, 1.8 Hz), 8.23 (d, 1H, J = 9 Hz), 8.61(d, 1H, J = 1.2 Hz), 9.35 (s, 1H). 363 783.5 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.84 (t, 3H, J = 7.2 Hz), 1.21 (m, 16H), 1.42 (m, 2H), 1.72 (m,10H), 2.00 (m, 3H), 2.24 (m, 5H), 2.64 (m, 1H), 2.79 (s, 3H), 2.97 (m,4H), 3.12 (m, 3H), 3.27 (m, 2H), 3.43 (m, 2H), 4.06 (t, 2H, J = 6.6 Hz),7.03 (t, 1H, J = 8.4 Hz), 7.56 (dd, 1H, J = 10.2, 2.4 Hz), 7.60 (d, 1H,J = 9 Hz), 7.74 (dd, 1H, J = 9, 1.8 Hz), 8.22 (d, 1H, J = 9 Hz), 8.57(d, 1H, J = 1.2 Hz), 9.29 (s, 1H). 364 799.5 ¹HNMR (600 MHz, CDCl₃, 25°C.): 0.85 (t, 3H, J = 7.2 Hz), 1.22 (m, 17H), 1.43 (m, 2H), 1.63 (m,3H), 1.78 (m, 11H), 2.34 (m, 2H), 2.52 (m, 2H), 2.73 (m, 4H), 2.81 (s,3H), 3.12 (m, 2H), 3.29 (m, 2H), 3.46 (m, 2H), 3.93 (m, 1H), 4.07 (t,2H, J = 6.6 Hz), 7.04 (t, 1H, J = 7.8 Hz), 7.58 (dd, 1H, J = 10.2, 1.8Hz), 7.62 (d, 1H, J = 8.4 Hz), 7.78 (dd, 1H, J = 9, 1.8 Hz), 8.23 (d,1H, J = 9 Hz), 8.57 (s, 1H), 9.58 (s, 1H). 365 773.5 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.82 (t, 3H, J = 7.2 Hz), 1.22 (m, 20H), 1.40 (m, 2H),1.78 (m, 6H), 2.67 (m, 1H), 2.79 (s, 3H), 2.90 (m, 6H), 3.11 (m, 4H),3.26 (m, 2H), 3.37 (m, 2H), 3.81 (m, 2H), 4.05 (t, 2H, J = 6.6 Hz), 7.04(t, 1H, J = 8.4 Hz), 7.54 (dd, 1H, J = 10.2, 2.4 Hz), 7.64 (d, 1H, J =8.4 Hz), 7.73 (dd, 1H, J = 9, 1.8 Hz), 8.23 (d, 1H, J = 9 Hz), 8.60 (s,1H), 9.34 (s, 1H). 366 811.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t,3H, J = 7.2 Hz), 1.24 (m, 20H), 1.42 (m, 2H), 1.82 (m, 8H), 2.06 (m,4H), 2.29 (m, 5H), 2.51 (m, 3H), 2.83 (s, 3H), 2.84 (m, 4H), 3.14 (m,6H)4.10 (t, 2H, J = 6.6 Hz), 7.18 (m, 1H), 7.49 (d, 1H, J = 9 Hz), 7.71(d, 1H, J = 6 Hz), 7.78 (d, 1H, J = 7.2 Hz), 8.23 (d, 1H, J = 8.4 Hz),8.51 (s, 1H), 9.18 (m, 1H). 367 827.5 ¹HNMR (600 MHz, CDCl₃, 25° C.):0.85 (t, 3H, J = 7.2 Hz), 1.22 (m, 20H), 1.40 (m, 2H), 1.63 (m, 3H),1.77 (m, 11H), 2.34 (m, 2H), 2.52 (m, 2H), 2.73 (m, 4H), 2.81 (s, 3H),3.12 (m, 2H), 3.29 (m, 2H), 3.46 (m, 2H), 3.93 (m, 1H), 4.07 (t, 2H, J =6.6 Hz), 7.04 (t, 1H, J = 7.8 Hz), 7.58 (dd, 1H, J = 10.2, 1.8 Hz), 7.62(d, 1H, J = 9 Hz), 7.78 (dd, 1H, J = 8.4, 1.2 Hz), 8.23 (d, 1H, J = 8.4Hz), 8.57 (d, 1H, J = 1.8 Hz), 9.28 (s, 1H). 368 828.5 ¹HNMR (600 MHz,CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.20 (m, 21H), 1.43 (m, 2H),1.81 (m, 6H), 1.92 (m, 4H), 2.42 (m, 2H), 2.72 (m, 8H), 2.81 (s, 3H),3.14 (m, 2H), 3.30 (m, 2H), 3.50 (m, 2H), 3.66 (t, 2H, J = 5.4 Hz), 4.07(t, 2H, J = 9 Hz), 7.05 (t, 1H, J = 9.6 Hz), 7.57 (dd, 1H, J = 10.2, 2.4Hz), 7.63 (d, 1H, J = 9 Hz), 7.78 (dd, 1H, J = 8.4, 1.8 Hz), 8.23 (d,1H, J = 8.4 Hz), 8.56 (d, 1H, J = 1.2 Hz), 9.27 (s, 1H). 369 856.5 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.22 (m, 23H), 1.44(m, 2H), 1.81 (m, 10H), 2.51 (m, 2H), 2.67 (m, 2H), 2.79 (m, 7H), 2.81(s, 3H), 3.21 (m, 2H), 3.31 (m, 2H), 3.49 (m, 2H), 3.69 (t, 2H, J = 5.4Hz), 4.07 (t, 2H, J = 9 Hz), 7.09 (t, 1H, J = 7.8 Hz), 7.56 (dd, 1H, J =10.2, 2.4 Hz), 7.64 (d, 1H, J = 9 Hz), 7.78 (dd, 1H, J = 8.4, 1.8 Hz),8.24 (d, 1H, J = 8.4 Hz), 8.57 (d, 1H, J = 1.2 Hz), 9.27 (s, 1H). 370798.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.24 (m,17H), 1.42 (m, 2H), 1.67 (m, 4H), 1.87 (m, 6H), 2.33 (m, 6H), 2.57 (m,8H), 2.80 (s, 3H), 3.07 (m, 2H), 3.29 (m, 2H), 3.46 (m, 2H), 4.06 (t,2H, J = 6.6 Hz), 7.03 (t, 1H, J = 8.4 Hz), 7.57 (dd, 1H, J = 10.2, 2.4Hz), 7.61 (d, 1H, J = 9 Hz), 7.78 (dd, 1H, J = 8.4, 1.8 Hz), 8.22 (d,1H, J = 9 Hz), 8.56 (d, 1H, J = 1.8 Hz), 9.27 (s, 1H). 371 826.5 ¹HNMR(600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.24 (m, 21H), 1.42(m, 2H), 1.61 (m, 2H), 1.71 (m, 2H), 1.80 (m, 6H), 2.31 (m, 6H), 2.51(m, 8H), 2.80 (s, 3H), 3.04 (m, 2H), 3.29 (m, 2H), 3.46 (m, 2H), 4.06(t, 2H, J = 6.6 Hz), 7.02 (t, 1H, J = 8.4 Hz), 7.58 (dd, 1H, J = 10.2,2.4 Hz), 7.61 (d, 1H, J = 9 Hz), 7.78 (dd, 1H, J = 8.4, 1.8 Hz), 8.22(d, 1H, J = 9 Hz), 8.57 (d, 1H, J = 1.8 Hz), 9.28 (s, 1H). 372 799.5¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.24 (m, 18H),1.39 (m, 3H), 1.78 (m, 10H), 2.24 (m, 2H), 2.40 (m, 4H), 2.69 (m, 1H),2.81 (s, 3H), 2.96 (m, 2H), 3.19 (m, 6H), 3.48 (m, 2H), 4.07 (t, 2H, J =6.6 Hz), 7.05 (d, 1H, J = 8.4 Hz), 7.57 (d, 1H, J = 10.2 Hz), 7.63 (d,1H, J = 8.4 Hz), 7.75 (d, 1H, J = 9 Hz), 8.23 (d, 1H, J = 9 Hz), 8.58(s, 1H), 9.27 (s, 1H). 373 827.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84(t, 3H, J = 7.2 Hz), 1.24 (m, 22H), 1.39 (m, 2H), 1.74 (m, 10H), 2.07(m, 2H), 2.16 (m, 4H), 2.65 (m, 2H), 2.81 (s, 3H), 3.01 (m, 4H), 3.29(m, 2H), 3.45 (m, 2H), 3.91 (m, 1H), 4.06 (t, 2H, J = 6.6 Hz), 7.05 (d,1H, J = 8.4 Hz), 7.57 (d, 1H, J = 10.2 Hz), 7.63 (d, 1H, J = 8.4 Hz),7.75 (d, 1H, J = 9 Hz), 8.23 (d, 1H, J = 9 Hz), 8.58 (s, 1H), 9.27 (s,1H). 374 781.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2 Hz),1.24 (m, 18H), 1.46 (m, 2H), 1.85 (m, 10H), 2.26 (m, 2H), 2.42 (m, 6H),2.78 (s, 3H), 2.97 (m, 2H), 3.20 (m, 6H), 3.45 (m, 2H), 3.99 (t, 2H, J =6.6 Hz), 6.97 (d, 2H, J = 9 Hz), 7.75 (d, 1H, J = 9.6 Hz), 7.78 (d, 2H,J = 9 Hz), 8.21 (d, 1H, J = 9 Hz), 8.56 (s, 1H), 9.25 (s, 1H). 375 809.6¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz), 1.21 (m, 22H),1.44 (m, 2H), 1.86 (m, 10H), 2.26 (m, 2H), 2.41 (m, 4H), 2.80 (s, 3H),3.01 (m, 2H), 3.20 (m, 7H), 3.48 (m, 2H), 3.99 (t, 2H, J = 6.6 Hz), 4.05(m, 1H), 6.97 (d, 2H, J = 9 Hz), 7.75 (dd, 1H, J = 8.4, 1.2 Hz), 7.79(d, 2H, J = 9 Hz), 8.21 (d, 1H, J = 9 Hz), 8.56 (s, 1H), 9.24 (s, 1H).376 783.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2 Hz), 1.22(m, 24H), 1.40 (m, 2H), 1.76 (m, 2H), 1.86 (m, 4H), 2.67 (m, 1H), 2.79(s, 3H), 3.21 (m, 7H), 3.33 (m, 7H), 3.94 (m, 2H), 3.99 (t, 2H, J = 6.6Hz), 6.97 (d, 2H, J = 9 Hz), 7.69 (m, 1H), 7.81 (d, 2H, J = 8.4 Hz),8.25 (d, 1H, J = 9 Hz), 8.64 (s, 1H), 9.41 (s, 1H). 377 821.6 ¹HNMR (600MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 7.2 Hz), 1.23 (m, 24H), 1.38 (m,2H), 1.77 (m, 2H), 1.87 (m, 10H), 2.23 (m, 2H), 2.32 (m, 2H), 2.69 (m,2H), 2.81 (s, 3H), 3.08 (m, 5H), 3.32 (m, 5H), 3.49 (m, 2H), 3.99 (t,2H, J = 6.6 Hz), 6.98 (d, 2H, J = 9 Hz), 7.65 (dd, 1H, J = 8.4, 1.2 Hz),7.78 (d, 2H, J = 9 Hz), 8.22 (d, 1H, J = 9 Hz), 8.53 (d, 1H, J = 1.2Hz), 9.23 (s, 1H) 378 837.5 ¹HNMR (600 MHz, CDCl₃, 25° C.): 0.85 (t, 3H,J = 7.2 Hz), 1.23 (m, 26H), 1.42 (m, 2H), 1.76 (m, 3H), 1.95 (m, 3H),2.04 (m, 3H), 2.29 (m, 4H), 2.68 (m, 2H), 2.82 (s, 3H), 3.08 (m, 5H),3.33 (m, 7H), 4.00 (t, 2H, J = 6 Hz), 4.19 (m, 1H), 7.00 (d, 2H, J = 8.4Hz), 7.77 (d, 1H, J = 9 Hz), 7.80 (d, 2H, J = 8.4 Hz), 8.22 (d, 1H, J =9 Hz), 8.53 (s, 1H), 9.27 (s, 1H) 380 713.5 ¹HNMR (400 MHz, CDCl₃, 25°C.): 0.84 (t, 3H, J = 6.8 Hz), 1.25 (m, 12H), 1.38 (m, 2H), 1.76 (m,2H), 1.86 (m, 4H), 2.69 (m, 1H), 2.79 (s, 3H), 2.90 (m, 6H), 3.09 (m,6H), 3.25 (m, 2H), 3.39 (m, 2H), 3.82 (m, 2H), 3.99 (t, 2H, J = 8.4 Hz),6.96 (d, 2H, J = 8.8 Hz), 7.71 (dd, 1H, J = 8.8, 1.6 Hz), 7.80 (d, 2H, J= 8.8 Hz), 8.23 (d, 1H, J = 8.8 Hz), 8.62 (d, 1H, J = 1.2 Hz), 9.35 (s,1H). 381 751.5 ¹HNMR (400 MHz, CDCl₃, 25° C.): 0.85 (t, 3H, J = 7.2 Hz),1.23 (m, 12H), 1.43 (m, 3H), 1.61 (m, 2H), 1.76 (m, 8H), 2.03 (m, 6H),2.20 (m, 2H), 2.33 (m, 2H), 2.67 (m, 1H), 2.80 (s, 3H), 3.05 (m, 4H),3.15 (m, 2H), 3.31 (m, 2H), 3.44 (m, 2H), 3.99 (t, 2H, J = 6.4 Hz), 6.97(d, 2H, J = 8.8 Hz), 7.74 (dd, 1H, J = 8.8, 1.6 Hz), 7.79 (d, 2H, J =8.8 Hz), 8.22 (d, 1H, J = 8.8 Hz), 8.58 (s, 1H), 9.27 (s, 1H). 382 767.5¹HNMR (400 MHz, CDCl₃, 25° C.): 0.84 (t, 3H, J = 6.8 Hz), 1.23 (m, 13H),1.39 (m, 3H), 1.75 (br m, 10H), 2.24 (m, 2H), 2.40 (m, 4H), 2.70 (m,1H), 2.81 (s, 3H), 2.99 (m, 3H), 3.20 (m, 6H), 3.48 (m, 2H), 3.99 (t,2H, J = 6.4 Hz), 4.02 (m, 1H), 6.97 (d, 2H, J = 8.8 Hz), 7.74 (dd, 1H, J= 8.8, 1.2 Hz), 7.79 (d, 2H, J = 8.8 Hz), 8.20 (d, 1H, J = 8.8 Hz), 8.57(s, 1H), 9.23 (s, 1H). 383 767.5 ¹HNMR (400 MHz, CDCl₃, 25° C.): 0.84(t, 3H, J = 6.8 Hz), 1.25 (m, 13H), 1.42 (m, 3H), 1.67 (m, 1H), 1.80 (brm, 8H), 2.09 (m, 5H), 2.65 (m, 2H), 2.82 (s, 3H), 2.92 (m, 6H), 3.34 (m,4H), 3.48 (m, 2H), 3.99 (t, 2H, J = 6.8 Hz), 4.14 (m, 1H), 6.99 (d, 2H,J = 8.8 Hz), 7.76 (dd, 1H, J = 8.8, 1.6 Hz), 7.79 (d, 2H, J = 8.8 Hz),8.21 (d, 1H, J = 8.8 Hz), 8.55 (s, 1H), 9.23 (s, 1H). 384 696.3 ¹HNMR(600 MHz, D₆-DMSO, 25° C.): 1.13 (m, 6H), 1.40 (m, 2H), 1.48 (br m, 9H),2.09 (m, 5H), 2.22 (m, 3H), 2.62 (m, 4H), 3.02 (m, 14H), 4.56 (t, 2H, J= 4.8 Hz), 7.11 (m, 1H), 7.18 (m, 1H), 7.75 (m, 1H), 7.79 (m, 3H), 8.03(m, 1H), 9.21 (m, 1H) 385 866.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.82(t, 3H, J = 7.2 Hz), 1.21 (m, 30H), 1.37 (m, 2H), 1.50 (m, 2H), 1.69 (m,5H), 1.90 (m, 2H), 2.66 (m, 8H), 2.85 (s, 3H), 3.02 (m, 7H), 3.57 (m,2H), 4.03 (t, 2H, J = 6.6 Hz), 4.65 (m, 1H), 7.13 (d, 2H, J = 8.4 Hz),7.82 (d, 2H, J = 8.4 Hz), 8.14 (d, 1H, J = 9 Hz), 8.28 (d, 1H, J = 8.4Hz), 8.48 (s, 1H), 9.38 (m, 1H). 386 836.5 ¹HNMR (600 MHz, D₆-DMSO, 25°C.): 0.82 (t, 3H, J = 7.2 Hz), 1.21 (m, 28H), 1.37 (m, 2H), 1.46 (m,4H), 1.69 (m, 4H), 1.85 (m, 2H), 2.32 (m, 5H), 2.61 (m, 8H), 2.85 (s,3H), 3.08 (m, 4H), 4.03 (t, 2H, J = 5.4 Hz), 7.11 (d, 2H, J = 8.4 Hz),7.81 (d, 2H, J = 7.8 Hz), 8.13 (d, 1H, J = 7.8 Hz), 8.27 (d, 1H, J = 9Hz), 8.49 (s, 1H), 9.37 (m, 1H). 387 884.5 ¹HNMR (600 MHz, D₆-DMSO, 25°C.): 0.81 (t, 3H, J = 7.2 Hz), 1.20 (m, 30H), 1.34 (m, 4H), 1.70 (m,5H), 1.84 (m, 2H), 2.35 (m, 3H), 2.66 (m, 7H), 2.85 (s, 3H), 3.00 (m,5H), 3.53 (m, 2H), 4.12 (t, 2H, J = 6 Hz), 4.54 (m, 1H), 7.38 (d, 1H, J= 7.2 Hz), 7.73 (m, 2H), 8.14 (d, 1H, J = 8.4 Hz), 8.28 (d, 1H, J = 9Hz), 8.49 (s, 1H), 9.38 (m, 1H). 388 854.5 ¹HNMR (600 MHz, D₆-DMSO, 25°C.): 0.81 (t, 3H, J = 7.2 Hz), 1.20 (m, 28H), 1.34 (m, 2H), 1.46 (m,4H), 1.62 (m, 4H), 1.70 (m, 2H), 2.20 (m, 6H), 2.41 (m, 3H), 2.52 (m,4H), 2.85 (s, 3H), 2.90 (m, 2H), 3.07 (m, 2H), 4.13 (t, 2H, J = 6 Hz),7.36 (t, 1H, J = 7.8 Hz), 7.69 (d, 1H, J = 7.8 Hz), 7.75 (d, 1H, J = 9.6Hz), 8.13 (d, 1H, J = 9 Hz), 8.27 (d, 1H, J = 9 Hz), 8.49 (s, 1H), 9.37(m, 1H). 389 855.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.82 (t, 3H, J =7.2 Hz), 1.21 (m, 28H), 1.39 (m, 3H), 1.45 (m, 2H), 1.71 (m, 9H), 1.90(m, 3H), 2.30 (m, 2H), 2.85 (s, 3H), 3.04 (m, 7H), 3.66 (m, 1H), 4.13(t, 2H, J = 6 Hz), 7.38 (t, 1H, J = 7.8 Hz), 7.72 (m, 1H), 7.78 (d, 1H,J = 10.8 Hz), 8.14 (d, 1H, J = 8.4 Hz), 8.29 (d, 1H, J = 8.4 Hz), 8.50(s, 1H), 9.38 (s, 1H). 390 840.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.82(t, 3H, J = 7.2 Hz), 1.07 (m, 3H), 1.20 (m, 20H), 1.37 (m, 2H), 1.42 (m,2H), 1.58 (m, 2H), 1.71 (m, 4H), 1.86 (m, 2H), 2.36 (m, 2H), 2.68 (m,9H), 2.85 (s, 3H), 3.08 (m, 5H), 3.32 (m, 4H), 4.12 (t, 2H, J = 6 Hz),7.38 (t, 1H, J = 8.4 Hz), 7.73 (d, 1H, J = 7.8 Hz), 7.77 (d, 1H, J =10.2 Hz), 8.15 (d, 1H, J = 9 Hz), 8.29 (d, 1H, J = 8.4 Hz), 8.49 (s,1H), 9.38 (s, 1H). 391 854.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.82 (t,3H, J = 7.2 Hz), 1.07 (m, 6H), 1.20 (m, 20H), 1.35 (m, 4H), 1.55 (m,2H), 1.71 (m, 4H), 1.85 (m, 2H), 2.33 (m, 3H), 2.68 (m, 8H), 2.85 (s,3H), 3.01 (m, 5H), 3.32 (m, 4H), 4.10 (t, 2H, J = 6 Hz), 7.38 (t, 1H, J= 8.4 Hz), 7.72 (d, 1H, J = 8.4 Hz), 7.77 (dd, 1H, J = 10.2, 1.8 Hz),8.15 (d, 1H, J = 9 Hz), 8.29 (d, 1H, J = 9 Hz), 8.50 (s, 1H), 9.38 (s,1H). 392 840.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.82 (t, 3H, J = 7.2Hz), 1.21 (m, 24H), 1.38 (m, 6H), 1.57 (m, 2H), 1.69 (m, 6H), 2.11 (m,2H), 2.36 (s, 3H), 2.64 (m, 2H), 2.69 (m, 2H), 2.75 (m, 4H), 2.84 (s,3H), 2.86 (m, 2H), 3.08 (m, 2H), 4.13 (t, 2H, J = 6 Hz), 7.35 (t, 1H, J= 8.4 Hz), 7.68 (d, 1H, J = 8.4 Hz), 7.76 (dd, 1H, J = 10.8, 1.8 Hz),8.14 (dd, 1H, J = 8.4, 0.6 Hz), 8.28 (d, 1H, J = 8.4 Hz), 8.50 (s, 1H),9.38 (s, 1H). 393 813.4 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.81 (t, 3H, J= 7.2 Hz), 1.19 (m, 24H), 1.37 (m, 2H), 1.48 (m, 2H), 1.72 (m, 3H), 1.87(m, 4H), 2.32 (m, 1H), 2.86 (s, 3H), 3.05 (m, 3H), 3.16 (m, 3H), 3.36(m, 4H), 3.60 (m, 4H), 4.12 (t, 2H, J = 6 Hz), 7.42 (t, 1H, J = 7.8 Hz),7.76 (m, 3H), 817 (d, 1H, J = 8.4 Hz), 8.30 (d, 1H, J = 8.4 Hz), 8.48(s, 1H), 9.40 (s, 1H) 394 840.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.82(t, 3H, J = 6.6 Hz), 1.09 (t, 3H, J = 6.6 Hz), 1.20 (m, 20H), 1.34 (m,4H), 1.61 (m, 6H), 1.84 (m, 2H), 2.31 (m, 2H), 2.45 (m, 1H), 2.68 (m,8H), 2.85 (s, 3H), 3.12 (m, 5H), 3.40 (m, 4H), 4.12 (t, 2H, J = 6 Hz),7.37 (t, 1H, J = 8.4 Hz), 7.70 (d, 1H, J = 8.4 Hz), 7.76 (dd, 1H, J =10.2, 1.2 Hz), 8.14 (d, 1H, J = 8.4 Hz), 8.28 (d, 1H, J = 8.4 Hz), 8.51(s, 1H), 9.38 (s, 1H). 395 826.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.81(t, 3H, J = 7.2 Hz), 1.20 (m, 22H), 1.34 (m, 2H), 1.44 (m, 4H), 1.66 (m,4H), 1.82 (m, 2H), 2.25 (m, 6H), 2.57 (m, 5H), 2.85 (s, 3H), 2.99 (m,4H), 3.35 (m, 4H), 4.05 (t, 2H, J = 6 Hz), 6.99 (dd, 1H, J = 7.2, 1.8Hz), 7.08 (d, 1H, J = 9 Hz), 8.08 (m, 1H), 8.15 (d, 1H, J = 8.4 Hz),8.29 (d, 1H, J = 9 Hz), 8.51 (s, 1H), 9.39 (s, 1H). 396 844.5 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 0.82 (t, 3H, J = 7.2 Hz), 1.21 (m, 24H), 1.32 (m,4H), 1.66 (m, 4H), 1.80 (m, 4H), 2.25 (m, 4H), 2.77 (m, 6H), 2.85 (s,3H), 3.05 (m, 5H), 3.35 (m, 2H), 4.28 (m, 2H), 7.82 (m, 2H), 8.18 (d,1H, J = 8.4 Hz), 8.33 (d, 1H, J = 8.4 Hz), 8.50 (s, 1H), 9.41 (s, 1H).397 844.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.80 (t, 3H, J = 7.2 Hz),1.21 (m, 24H), 1.35 (m, 6H), 1.67 (m, 2H), 1.72 (m, 2H), 1.80 (m, 2H),2.22 (m, 4H), 2.44 (m, 3H), 2.54 (m, 4H), 2.85 (s, 3H), 2.96 (m, 2H),3.10 (m, 2H), 3.35 (m, 2H), 4.19 (t, 2H, J = 6.6 Hz), 7.34 (t, 1H, J =7.2 Hz), 7.93 (m, 1H), 7.16 (d, 1H, J = 9 Hz), 8.29 (d, 1H, J = 9 Hz),8.52 (s, 1H), 9.38 (s, 1H). 398 864.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.):0.82 (t, 3H, J = 7.2 Hz), 1.21 (m, 32H), 1.45 (m, 9H), 1.69 (m, 4H),1.85 (m, 3H), 2.32 (m, 5H), 2.58 (m, 6H), 2.85 (s, 3H), 3.08 (m, 4H),4.03 (t, 2H, J = 6 Hz), 7.11 (d, 2H, J = 8.4 Hz), 7.80 (d, 2H, J = 8.4Hz), 8.13 (d, 1H, J = 8.4 Hz), 8.27 (d, 1H, J = 9 Hz), 8.49 (s, 1H),9.36 (s, 1H) 399 882.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.84 (t, 3H, J= 7.2 Hz), 1.21 (m, 32H), 1.33 (m, 7H), 1.73 (m, 4H), 1.90 (m, 4H), 2.32(m, 4H), 2.58 (m, 6H), 2.85 (m, 5H), 3.09 (m, 4H), 4.14 (m, 2H), 7.39(m, 1H), 7.73 (m, 2H), 8.15 (m, 1H), 8.27 (m, 1H), 8.49 (s, 1H), 9.38(s, 1H) 400 829.4 ¹HNMR (600 MHz, D₆-DMSO, 25° C.) 0.81 (t, 3H, J = 7.2Hz), 1.17 (m, 25H), 1.35 (m, 4H), 1.70 (m, 7H), 2.60 (m, 4H), 2.70 (m,4H), 2.85 (s, 3H), 3.10 (m, 6H), 4.12 (t, 2H, J = 6.6 Hz), 7.40 (t, 1H,J = 6.6 Hz), 7.76 (d, 2H, J = 10.2 Hz), 8.16 (d, 1H, J = 8.4 Hz), 8.29(d, 1H, J = 8.4 Hz), 8.49 (s, 1H), 9.39 (s, 1H). 401 854.4 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 0.82 (t, 3H, J = 7.2 Hz), 1.24 (m, 22H), 1.35 (m,2H), 1.44 (m, 2H), 1, 71 (br m, 7H), 1.98 (s, 3H), 2.40 (m, 4H), 2.85(s, 3H), 3.09 (m, 4H), 3.33 (m, 6H), 3.41 (m, 3H), 4.12 (t, 2H, J = 6.6Hz), 7.38 (t, 1H, J = 8.4 Hz), 7.74 (d, 1H, J = 7.8 Hz), 7.77 (d, 1H, J= 10.8 Hz), 8.15 (d, 1H, J = 9 Hz), 8.29 (d, 1H, J = 9 Hz), 8.49 (s,1H), 9.39 (s, 1H). 402 842.4 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.82 (t,3H, J = 7.2 Hz), 1.22 (m, 24H), 1.37 (m, 2H), 1.57 (m, 2H), 1.72 (m,4H), 1.93 (m, 5H), 2.53 (m, 4H), 2.77 (m, 8H), 3.24 (m, 7H), 4.13 (t,2H, J = 6.6 Hz), 7.41 (t, 1H, J = 7.8 Hz), 7.79 (d, 2H, J = 9 Hz), 8.36(m, 2H), 8.68 (s, 1H), 9.41 (s, 1H). 411 812.5 ¹HNMR (600 MHz, D₆-DMSO,25° C.): 0.82 (t, 3H, J = 7.2 Hz), 1.01 (m, 3H), 1.21 (m, 18H), 1.31 (m,6H), 1.62 (m, 2H), 1.71 (m, 2H), 1.90 (m, 2H), 2.18 (m, 3H), 2.42 (m,4H), 2.53 (m, 4H), 2.85 (s, 3H), 2.90 (m, 2H), 3.08 (m, 2H), 3.29 (m,3H), 4.13 (t, 2H, J = 6 Hz), 7.36 (t, 1H, J = 8.4 Hz), 7.70 (d, 1H, J =8.4 Hz), 7.76 (d, 1H, J = 10.2 Hz), 8.14 (d, 1H, J = 9 Hz), 8.28 (d, 1H,J = 9 Hz), 8.50 (s, 1H), 9.38 (s, 1H). 412 826.5 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 0.82 (t, 3H, J = 6.6 Hz), 1.08 (m, 6H), 1.21 (m, 20H),1.38 (m, 5H), 1.72 (m, 5H), 1.85 (m, 3H), 2.21 (m, 2H), 2.70 (m, 6H),2.85 (s, 3H), 3.09 (br m, 6H), 4.13 (t, 2H, J = 6.6 Hz), 7.38 (m, 1H),7.73 (m, 1H), 7.77 (d, 1H, J = 8.4 Hz), 8.15 (d, 1H, J = 8.4 Hz), 8.29(d, 1H, J = 9 Hz), 8.50 (s, 1H), 9.38 (s, 1H). 413 812.5 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 0.81 (t, 3H, J = 7.2 Hz), 1.01 (m, 3H), 1.21 (m, 18H),1.33 (m, 4H), 1.54 (m, 4H), 1.70 (m, 2H), 1.84 (m, 2H), 2.38 (m, 4H),2.52 (m, 7H), 2.85 (s, 3H), 3.11 (m, 4H), 3.27 (m, 3H), 4.13 (t, 2H, J =6.6 Hz), 7.37 (t, 1H, J = 8.4 Hz), 7.70 (d, 1H, J = 8.4 Hz), 7.77 (dd,1H, J = 10.8, 1.8 Hz), 8.13 (dd, 1H, J = 9, 1.2 Hz), 8.28 (d, 1H, J =8.4 Hz), 8.51 (s, 1H), 9.38 (s, 1H). 414 868.5 ¹HNMR (600 MHz, D₆-DMSO,25° C.): 0.82 (t, 3H, J = 7.2 Hz), 1.01 (m, 3H), 1.21 (m, 28H), 1.35 (m,6H), 1.64 (m, 2H), 1.72 (m, 2H), 1.81 (m, 2H), 2.22 (m, 6H), 2.57 (m,5H), 2.85 (s, 3H), 2.95 (m, 2H), 3.08 (m, 2H), 3.29 (m, 1H), 4.12 (t,2H, J = 6 Hz), 7.37 (t, 1H, J = 8.4 Hz), 7.71 (d, 1H, J = 5.4 Hz), 7.76(d, 1H, J = 10.2 Hz), 8.14 (d, 1H, J = 8.4 Hz), 8.28 (d, 1H, J = 8.4Hz), 8.50 (s, 1H), 9.38 (s, 1H). 415 882.5 ¹HNMR (600 MHz, D₆-DMSO, 25°C.): (m, 5H), 1.85 (m, 2H), 2.20 (m, 3H), 2.62 (m, 6H), 2.85 (s, 3H),2.95 (m, 3H), 3.08 (m, 3H), 4.13 (t, 2H, J = 6.6 Hz), 7.37 (t, 1H, J =7.8 Hz), 7.72 (m, 1H), 7.76 (dd, 1H, J = 10.2, 1.2 Hz), 8.14 (d, 1H, J =8.4 Hz), 8.29 (d, 1H, J = 8.4 Hz), 8.50 (s, 1H), 9.38 (s, 1H). 416 869.5¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.81 (t, 3H, J = 7.2 Hz), 1.20 (m,32H), 1.35 (m, 5H), 1.60 (m, 2H), 1.71 (m, 2H), 1.89 (m, 2H), 2.38 (m,3H), 2.54 (m, 6H), 2.85 (s, 3H), 2.95 (m, 2H), 3.12 (m, 4H), 4.12 (t,2H, J = 6.6 Hz), 7.37 (t, 1H, J = 7.8 Hz), 7.71 (m, 1H), 7.76 (dd, 1H, J= 10.2, 1.8 Hz), 8.14 (d, 1H, J = 8.4 Hz), 8.27 (d, 1H, J = 9 Hz), 8.51(s, 1H), 9.37 (s, 1H). 417 816.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.80(t, 3H, J = 7.2 Hz), 1.20 (m, 18H), 1.35 (m, 6H), 1.63 (m, 2H), 1.72 (m,5H), 2.18 (m, 6H), 2.38 (m, 4H), 2.55 (m, 2H), 2.85 (s, 3H), 2.90 (m,2H), 3.11 (m, 2H), 3.28 (m, 2H), 4.19 (t, 2H, J = 6 Hz), 7.33 (t, 1H, J= 7.8 Hz), 7.92 (m, 1H), 8.16 (d, 1H, J = 8.4 Hz), 8.29 (d, 1H, J = 9Hz), 8.52 (s, 1H), 9.38 (s, 1H). 418 830.5 ¹HNMR (600 MHz, D₆-DMSO, 25°C.): 0.80 (t, 3H, J = 7.2 Hz), 1.02 (m, 3H), 1.20 (m, 18H), 1.37 (m,6H), 1.75 (m, 6H), 2.20 (m, 6H), 2.55 (m, 6H), 2.85 (s, 3H), 2.90 (m,2H), 3.11 (m, 2H), 3.31 (m, 2H), 4.19 (t, 2H, J = 6.6 Hz), 7.36 (m, 1H),7.94 (m, 1H), 8.16 (d, 1H, J = 9 Hz), 8.29 (d, 1H, J = 9 Hz), 8.52 (s,1H), 9.38 (s, 1H). 419 844.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.80 (t,3H, J = 7.2 Hz), 1.19 (m, 24H), 1.38 (m, 3H), 1.47 (m, 3H), 1.74 (m,3H), 1.90 (m, 6H), 2.74 (m, 6H), 2.85 (s, 3H), 2.89 (m, 2H), 3.12 (m,4H), 3.31 (m, 2H), 4.19 (t, 2H, J = 6.6 Hz), 7.39 (m, 1H), 7.90 (m, 1H),8.17 (d, 1H, J = 7.2 Hz), 8.30 (d, 1H, J = 7.2 Hz), 8.52 (s, 1H), 9.39(s, 1H). 420 830.4 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.81 (t, 3H, J =7.2 Hz), 1.09 (m, 3H), 1.21 (m, 20H), 1.39 (m, 5H), 1.65 (m, 4H), 1.72(m, 2H), 1.84 (m, 2H), 2.44 (m, 4H), 2.55 (m, 5H), 2.85 (s, 3H), 3.16(m, 4H), 3.31 (m, 2H), 4.20 (t, 2H, J = 6.6 Hz), 7.34 (t, 1H, J = 7.8),7.91 (m, 1H), 8.16 (d, 1H, J = 9 Hz), 8.29 (d, 1H, J = 8.4 Hz), 8.53 (s,1H), 9.37 (s, 1H). 421 858.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.83 (t,3H, J = 6.6 Hz), 1.22 (m, 33H), 1.66 (m, 6H), 2.15 (m, 6H), 2.61 (m,4H), 2.86 (m, 7H), 3.09 (m, 3H), 4.21 (t, 2H, J = 6 Hz), 7.80 (m, 2H),8.18 (d, 1H, J = 7.8 Hz), 8.33 (d, 1H, J = 8.4 Hz), 8.50 (s, 1H), 9.41(s, 1H). 422 872.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.81 (t, 3H, J =7.2 Hz), 1.20 (m, 34H), 1.77 (m, 5H), 1.99 (m, 6H), 2.68 (m, 4H), 2.85(m, 8H), 3.15 (m, 3H), 4.19 (t, 2H, J = 6 Hz), 7.41 (m, 1H), 7.93 (m,1H), 8.18 (m, 1H), 8.32 (m, 1H), 8.51 (s, 1H), 9.40 (s, 1H). 432 858.5¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.83 (t, 3H, J = 6.6 Hz), 1.22 (m,35H), 1.65 (m, 6H), 2.16 (m, 3H), 2.61 (m, 3H), 2.86 (m, 7H), 3.16 (m,4H), 4.21 (t, 2H, J = 6 Hz), 7.80 (m, 2H), 8.18 (d, 1H, J = 7.8 Hz),8.33 (d, 1H, J = 8.4 Hz), 8.50 (s, 1H), 9.14 (s, 1H). 433 872.5 ¹HNMR(600 MHz, D₆-DMSO, 25° C.): 0.82 (t, 3H, J = 7.2 Hz), 1.20 (m, 36H),1.66 (m, 4H), 1.90 (m, 5H), 2.74 (m, 5H), 2.86 (m, 6H), 3.04 (m, 4H),4.21 (t, 2H, J = 6.6 Hz), 7.81 (m, 2H), 8.19 (d, 1H, J = 8.4 Hz), 8.32(d, 1H, J = 9 Hz), 8.50 (s, 1H), 9.40 (s, 1H). 451 794.17 ¹HNMR (600MHz, D₆-DMSO, 25° C.): 0.84 (t, 3H, J = 7.8 Hz), 1.07 (m, 3H), 1.22 (m,18H), 1.37 (m, 6H), 1.69 (m, 4H), 1.72 (m, 4H), 1.86 (m, 2H), 2.40 (m,4H), 2.60 (m, 5H), 2.85 (s, 3H), 3.09 (m, 3H), 3.17 (m, 2H), 4.05 (t,2H, J = 6 Hz), 7.11 (d, 2H, J = 8.4 Hz), 7.80 (d, 2H, J = 7.2 Hz), 8.14(d, 1H, J = 8.4 Hz), 8.28 (d, 1H, J = 7.8 Hz), 8.49 (s, 1H), 9.38 (s,1H). 452 808.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.84 (t, 3H, J = 7.2Hz), 1.07 (m, 6H), 1.22 (m, 18H), 1.37 (m, 7H), 1.69 (m, 4H), 1.72 (m,3H), 2.19 (m, 3H), 2.60 (m, 7H), 2.85 (s, 3H), 2.96 (m, 2H), 3.09 (m,3H), 4.05 (t, 2H, J = 6.6 Hz), 7.12 (d, 2H, J = 8.4 Hz), 7.81 (d, 2H, J= 7.8 Hz), 8.14 (d, 1H, J = 8.4 Hz), 8.28 (d, 1H, J = 8.4 Hz), 8.49 (s,1H), 9.37 (s, 1H). 453 822.4 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.84 (t,3H, J = 7.2 Hz), 1.01 (m, 3H), 1.22 (m, 22H), 1.39 (m, 7H), 1.69 (m,2H), 1.72 (m, 3H), 1.84 (m, 2H), 2.16 (m, 7H), 2.61 (m, 5H), 2.85 (s,3H), 2.91 (m, 2H), 3.09 (m, 2H), 4.04 (t, 2H, J = 6.6 Hz), 7.11 (d, 2H,J = 8.4 Hz), 7.79 (d, 2H, J = 8.4 Hz), 8.13 (d, 1H, J = 8.4 Hz), 8.27(d, 1H, J = 9 Hz), 8.50 (s, 1H), 9.37 (s, 1H). 454 836.5 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 0.84 (m, 3H), 1.22 (m, 34H), 1.48 (m, 2H), 1.71 (m,4H), 1.91 (m, 3H), 2.31 (m, 3H), 2.61 (m, 4H), 2.85 (m, 6H), 3.09 (m,4H), 4.05 (m, 2H), 7.13 (d, 2H, J = 5.4 Hz), 7.82 (m, 2H), 8.14 (m, 1H),8.28 (m, 1H), 8.49 (s, 1H), 9.37 (s, 1H). 457 878.4 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 0.84 (t, 3H, J = 7.2 Hz), 0.97 (t, 3H, J = 6.6 Hz),1.23 (m, 34H), 1.36 (m, 6H), 1.57 (m, 2H), 1.70 (m, 2H), 1.76 (m, 2H),2.11 (m, 3H), 2.30 (m, 6H), 2.85 (s, 3H), 2.88 (m, 2H), 3.09 (m, 3H),4.05 (t, 2H, J = 6 Hz), 7.01 (d, 2H, J = 9 Hz), 7.78 (d, 2H, J = 8.4Hz), 8.12 (dd, 1H, J = 9, 1.2 Hz), 8.27 (d, 1H, J = 8.4 Hz), 8.49 (d,1H, J = 1.2 Hz), 9.37 (s, 1H). 458 878.4 ¹HNMR (600 MHz, D₆-DMSO, 25°C.): 0.84 (t, 3H, J = 7.2 Hz), 0.96 (m, 3H), 1.21 (m, 34H), 1.38 (m,6H), 1.62 (m, 2H), 1.70 (m, 2H), 1.81 (m, 2H), 2.22 (m, 3H), 2.41 (m,6H), 2.85 (s, 3H), 2.94 (m, 2H), 3.08 (m, 3H), 4.05 (t, 2H, J = 6 Hz),7.11 (d, 2H, J = 8.4 Hz), 7.79 (d, 2H, J = 9 Hz), 8.13 (dd, 1H, J = 9,1.2 Hz), 8.27 (d, 1H, J = 9 Hz), 8.49 (s, 1H), 9.37 (s, 1H). 459 890.5¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.29 (d, 4H, J = 9 Hz), 0.83 (t, 3H, J= 7.2 Hz), 1.18 (m, 38H), 1.37 (m, 2H), 1.54 (m, 4H), 1.72 (m, 2H), 1.82(m, 2H), 2.00 (m, 4H), 2.64 (m, 7H), 2.85 (s, 3H), 4.04 (t, 2H, J = 6Hz), 7.14 (d, 2H, J = 8.4 Hz), 7.84 (d, 2H, J = 7.8 Hz), 8.16 (d, 1H, J= 9 Hz), 8.30 (d, 1H, J = 8.4 Hz), 8.48 (s, 1H), 9.40 (s, 1H). 460 890.5¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.29 (d, 4H, J = 9 Hz), 0.83 (t, 3H, J= 7.2 Hz), 1.18 (m, 38H), 1.39 (m, 2H), 1.54 (m, 4H), 1.72 (m, 2H), 1.82(m, 2H), 2.00 (m, 4H), 2.64 (m, 7H), 2.85 (s, 3H), 4.06 (t, 2H, J = 6.6Hz), 7.14 (d, 2H, J = 8.4 Hz), 7.84 (d, 2H, J = 7.8 Hz), 8.16 (d, 1H, J= 8.4 Hz), 8.30 (d, 1H, J = 8.4 Hz), 8.48 (s, 1H), 9.40 (s, 1H). 461892.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.84 (m, 3H), 1.22 (m, 38H),1.70 (m, 8H), 2.35 (m, 7H), 2.60 (m, 5H), 2.84 (m, 4H), 3.12 (m, 6H),4.05 (m, 2H), 7.12 (m, 2H), 7.82 (m, 2H), 8.15 (m, 1H), 8.29 (m, 1H),8.49 (s, 1H), 9.37 (s, 1H). 462 907.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.):0.83 (t, 3H, J = 7.2 Hz), 1.09 (m, 3H), 1.22 (m, 38H), 1.37 (m, 4H),1.65 (m, 4H), 1.72 (m, 2H), 1.84 (m, 2H), 2.44 (m, 4H), 2.55 (m, 3H),2.85 (m, 8H), 3.20 (m, 2H), 4.04 (t, 2H, J = 6 Hz), 7.11 (d, 2H, J = 9Hz), 7.79 (d, 2H, J = 9 Hz), 8.13 (dd, 1H, J = 8.4, 1.2 Hz), 8.27 (d,1H, J = 9 Hz), 8.50 (s, 1H), 9.36 (s, 1H). 465 943.2 ¹HNMR (600 MHz,D₆-DMSO, 25° C.): 0.84 (m, 3H), 1.21 (m, 38H), 1.35 (m, 6H), 1.65 (m,4H), 1.72 (m, 2H), 1.84 (m, 2H), 2.28 (m, 7H), 2.55 (m, 6H), 2.85 (s,4H), 3.09 (m, 3H), 4.05 (m, 2H), 7.11 (d, 2H, J = 7.2 Hz), 7.80 (d, 2H,J = 5.4 Hz), 8.13 (d, 1H, J = 6 Hz), 8.28 (d, 1H, J = 7.2 Hz), 8.49 (s,1H), 9.37 (s, 1H). 466 934.5 ¹HNMR (600 MHz, D₆-DMSO, 25° C.): 0.84 (t,3H, J = 7.2 Hz), 1.09 (m, 3H), 1.22 (m, 40H), 1.37 (m, 4H), 1.65 (m,4H), 1.72 (m, 3H), 1.84 (m, 2H), 2.44 (m, 4H), 2.55 (m, 4H), 2.85 (m,8H), 3.10 (m, 2H), 4.05 (t, 2H, J = 6 Hz), 7.12 (m, 2H), 7.81 (m, 2H),8.14 (m, 1H), 8.28 (m, 1H), 8.50 (s, 1H), 9.37 (s, 1H). *LC-MS: (m/z,[M + H]+). ** MS salt: mesylate salt

BIOLOGICAL EXAMPLES Biological Example 1. Killing Pathogenic BloodVessels by Targeting PLXDC1/PLXDC2

Pathogenic angiogenesis plays a key role in several major humandiseases. In addition to tumor growth and metastasis, angiogenesis is amajor pathogenic driving force in several blinding diseases includingdiabetic retinopathy, age-related macular degeneration (AMD), andretinopathy of prematurity. AMD and diabetic retinopathy are the leadingcauses of blindness in the elderly and populations at the working age inthe United States, respectively. Retinopathy of prematurity is a commonreason that causes the loss of vision for newborn babies. Pathogenicblood vessels are blood vessels that exist in the diseased states suchtumor blood vessels in tumors and new blood vessels in AMD or diabeticretinopathy that are distinct from healthy blood vessels in the eye (asdemonstrated in FIG. 1). PLXDC1 expression was highly enriched inpathogenic blood vessels in a mouse model of CNV (laser-inducedchoroidal neovascularization (CNV) (FIG. 1A-D), in pathogenic bloodvessels in a mouse model of ischemia-induced retinopathy, but not inblood vessels of healthy retina (FIG. 1E-H).

Pathogenic blood vessels differ from healthy blood vessels not only intissue location and health state, but also in function. Pathogenic bloodvessels drive pathogenic processes. For example, tumor blood vesselsdrive tumor growth and supply tumor with oxygen and nutrients that areessential for its survival. Choroidal neovascularization, the pathogenicblood vessels in AMD, cause blindness due to leakage that kills healthyneurons. While there are current therapeutic strategies for inhibitingthe growth of new blood vessels, such as anti-angiogenesis therapies,there are no known strategies for destroying already existing pathogenicblood vessels. The compounds disclosed herein can kill existingpathogenic blood vessels, thus providing an improvement over existinganti-angiogenic therapies.

Two markers of pathogenic blood vessels, PLXDC1 (TEM7) and PLXDC2 arehighly specifically expressed in the tumor blood vessels of diversetypes of cancer, and in the pathogenic blood vessels in diabeticretinopathy. This highly specific expression in pathogenic blood vesselsis especially well documented for TEM7 (=Tumor Endothelial Marker 7),which was first described in 2000. This high enrichment is not presentin healthy blood vessels. High PLXDC1 expression has now been identifiedin choroidal neovascularization (pathogenic angiogenesis in AMD) andischemia-induced retinopathy (pathogenic angiogenesis in retinopathy ofprematurity) (FIG. 1). The striking enrichment of PLXDC1 in thepathogenic blood vessels in several diseases is summarized in the tablebelow:

Highly specific expression in pathogenic blood Pathogenic angiogenesisvessels References Tumor blood vessles in Yes St Croix et al., 2000diverse types of cancer Carson-Walter et al., 2001 Bagley et al., 2011Diabetic retinopathy Yes Yamaji et al., 2008 Choroidal Yes FIG. 1neovascularization Ischemia-induced Yes FIG. 1 retinopathy Yamaji, Y.,et al. (2008). Invest Ophthalmol Vis Sci 49, 3151-3157 Bagley et al.,(2011) Microvasc Res. November; 82(3): 253-62 Carson-Walter E. B. etal., Cancer Res. 2001; 61(18): 6649-55. St Croix, B., et al. (2000).Science 289, 1197-1202.

Although PLXDC1/PLXDC2 were known markers of pathogenic blood vessels,it was not known how to effectively target and kill the existingpathogenic blood vessels. In fact, anti-PLXDC1 antibodies have beendeveloped as a potential anti-angiogenic therapy. In Bagley et al.,Microvasc Res. 2011 November; 82(3):253-62, an anti-PLXDC1 antibody wasidentified that mediated antibody-dependent cellular cytotoxicity (ADCC)and phagocytosis. Such cancer immunotherapy approaches, however, havenot yielded positive therapeutic results. Furthermore, PigmentEpithelium Derived Factor (PEDF), a natural ligand for PLXDC1 and PLXDC2with anti-angiogenic properties, failed to kill existingPLXDC-expressing blood vessels. This example demonstrates that agentsthat modulate the PLXDC1/PLXDC2 receptor can effectively kill existingblood vessels.

FIG. 2 demonstrates that compound 369 targeting PLXDC1/PLXDC2 can killthe endothelial cells in an ex vivo model of choroidalneovascularization (see, for example, Shao, Z. et al., PLoS One. 2013Jul. 26; 8(7):e69552, which is herein incorporated by reference) withoutaffecting the healthy tissue (choroid and RPE).

Biological Example 2: Establishment of an Ex Vivo Primary TumorAngiogenesis Model

This example describes a procedure to prepare a primary tumorangiogenesis model for assessing the efficacy of anti-cancer candidateagents.

Protocol:

1. The day before the experiment, spray all necessary tools with 70%ethanol and sterilize them under UV light overnight, including blade,dissecting and micro-dissecting scissors and biceps. Place 24-welldishes at 4° C. to pre-chill plates and thaw Matrigel 24 hours beforetumor dissection.

2. Spray 70% ethanol on working bench. Prepare two sterile petri disheswith 10 mL sterile PBS. Steps 3 and 4 are for mouse tumor models. Forfresh human tumor, directly go to step 5.

3. Euthanize the tumor-bearing mice. Spray 70% ethanol on the mouse andremove the tumor using sterilized dissecting tools (avoid the fur).Rinse the tumor in petri dish with sterile PBS to remove ethanol andfur. Transfer the tumor to a new petri dish with PBS for dissection.Place the dish on ice.

4. Using pre-chilled sterile pipet tips to seed regular Matrigel in 24well plates on ice. Matrigel (30 μL) is dropped in the middle of eachwell without touching the edge of the well (avoid introducing bubbles ifpossible).

5. Cut the tumor in halves using the sterile blade. Identify and isolatehealthy tumor tissue that is not necrotic and is within the tumorcapsule. Cut the healthy tumor tissue into small pieces. For instance, asuitable size for the tumor tissue is 0.5 mm (H)×0.5 mm (L)×0.3 mm (D)with a total volume of 0.075 mm³.

6. Gently transfer and embed each tumor piece in the Matrigel drop inthe 24-well plate. Place the embedded piece in the bottom and middle ofeach Matrigel drop. Keep the plate on ice all the time.

7. After seeding the tumor pieces, plates are incubated in a 37° C. cellculture incubator without medium for 10 minutes in order for theMatrigel to solidify.

8. Endothelial Growth Medium (0.5 mL) is added to each well andincubated at 37° C. with 5% CO₂. Wait until the new endothelial cellshave grown out of the tumor or are larger than 3 mm in diameter untiltreatment. This usually takes 4 days for the LL2 Lewis lung cancer modeland 7 days for the CT26 colon cancer model. For human tumor models, thegrowth time is typically 2-3 weeks, depending on the tumor type. Mediais changed every 4 days during prolonged culture. Typically, when thetumor tissue grows to 2 mm in diameter, it is good for drug testing. Asize of about 3 mm in diameter can make visualization easier.

9. When the assay is ready to be analyzed for cell death (e.g., 48 hoursafter drug addition), prepare the dye mixture by mixing 6 μL of greendye to stain live cells (5 mg/mL Fluorescein diacetate or FDA in DMSO)with 30 μL of red dye (2.5 mg/mL Propidium iodide or PI in PBS) to staindead cells in an Eppendorf tube. The FDA dye needs to be stored frozenin a −20° C. freezer because it has a labile ester bond.

10. Add 1 μL of the dye mixture to each well of the 24-well dish. It isusually performed one 24-well dish at a time given the amount of timeneeded to take pictures (the green dye is not as stable in the cells inthe long term).

11. Gently rock the dish a few times to mix the dye with the media inthe wells and incubate the dish at 37° C. for 10 min (too longincubation can make the green signal too intense).

12. Wash each well with 0.5 mL of sterile PBS and then add 0.5 mL ofphenol red free SFM to each well. Alternatively 0.5 mL of regularEndothelial Cell Growth Media can be added to each well if this wellneeds to be continuously maintained after the experiment.

13. Look through all wells on an inverted microscope using the 2×objective lens to observe morphological changes.

14. Taking pictures in the red and green channels would allow not onlythe recording of the result but also more accurate quantitation of theresult. To take pictures for all the wells, first pick a well that hasrobust red and green signals. Take a picture at the red channel usingthe optimal setting (remember this setting) and then take a picture atthe green channel using another optimal setting (remember this setting).The final picture is the merged picture of the red and green channels.Take all other wells in each channel using the same settings so thatdifferent wells can be compared.

Cells having green color are live cells and cells having red color aredead cells. A portion of the tumor is yellow, emitted from red cellsmixed with green cells. The cell death in the tumor block is likely dueto hypoxia in the middle of the tumor that caused cell death over time,which is unrelated to drug treatment. New tumor endothelial cells thatare outside of the tumor block in this model allows direct visualizationand the quantitation of their growth and killing by an agent (either acompound or a biologic drug) described herein. The samples treated withthe compounds show dead endothelial cells in red, whereas theendothelial cells of untreated samples are green. The percent cell deathis calculated according the ratio of the red area and total endothelialcell area.

Biological Example 3: Mouse Colon Cancer Model Drug Testing:

A tumor from xenograft mouse model of colon cancer (CT26.CL25) was grownusing the method described herein to establish an ex vivo model of tumorangiogenesis. Treatment did not start until the new tumor endothelialcells had grown for 7 days. After drug treatment was done for two days,cell survival was assessed by a two-color assay using a mixture offluorescein diacetate (green dye) and propidium iodide (red dye). Greencells represented live cells. Red cells represented dead cells. Orangecells represented a mixture of live and dead cells.

The percent cell death is calculated according the ratio of the red areaand total endothelial cell area.

The activity of the tested compounds is provided in Table 3 below.Morphology observations after 48 hours are provided under the column “48hrs,” wherein: “0” indicates all cells have normal endothelial cellmorphology (cells are elongated and connect to neighbor cells); “*”indicates 50% or less of cells vesicularize in cell shape; “**”indicates more than 50% but less than 100% of endothelial cellsvesicularize in cell shape; “***” indicates 100% of endothelial cellsvesicularize in cell shape; “****” indicates 100% of endothelial cellsvesicularize in cell shape and look flattened in morphology (indicatingdisintegration of the cell body). Vesicularization in cell shapeindicates that the endothelial cells no longer have the elongated shapeand no longer connect to neighbor cells.

TABLE 3 Colon CT26 ex vivo model of tumor angiogenesis No 48 hrs Celldeath Conc. (μm) 42 0  0% 40 43 *** 90% 40 44 0  0% 40 45 0  0% 40 46**** 100%  40 47 0 10% 40 48 0 10% 40 49 0 10% 40 50 *** 100%  40 51 ***20% 40 52 0  0% 40 54 0 10% 40 55 0 50% 40 56 0 30% 40 57 * 60% 40 58 *50% 40 59 0 50% 40 60 0  5% 40 61 0 20% 40 62 ** 70% 40 63 *** 70% 40 64*** 100%  40 65 0  0% 40 66 0  0% 40 67 0  0% 40 68 ** 50% 40 69 0  0%40 70 0 10% 40 71 0  0% 40 72 0  0% 40 73 0  0% 40 74 *** 100%  40 75 0 0% 40 76 ** 100%  40 77 0 40% 40 78 0  0% 40 79 *** 100%  10 80 ***100%  10 81 0  0% 40 82 0 10% 40 84 * 100%  40 85 0 50% 40 86 *** 100% 10 87 0  0% 40 88 *** 60% 40 89 *** 100%  10 90 0  0% 40 91 *** 100%  1092 0  0% 40 93 *** 100%  10 94 0  0% 40 95 0  0% 40 96 0  0% 10 97 ***100%  10 98 *** 50% 10 99 0  0% 40 100 **** 100%  40 101 * 50% 20 102 0 5% 40 110 ** 10% 40 112 ** 10% 40 116 * 50% 20 117 *** 100%  20 118 ***100%  20 119 0 50% 20 121 *** 40% 40 123 0 20% 40 124 0 20% 40 128 0 10%40 129 0  0% 40 130 0 40% 40 131 ** 50% 40 132 * 40% 40 135 0 30% 40 1360 30% 40 137 0 40% 40 138 0 20% 40 139 0 40% 40 140 ** 60% 40 144 0 30%40 145 0 30% 40 146 0  0% 40 147 0  0% 40 148 0  0% 40 149 * 20% 40 1500 10% 40 151 **** 100%  40 152 ** 30% 40 153 * 20% 40 154 * 30% 40 155*** 20% 40 156 0  0% 40 157 **** 60% 40 158 **** 100%  40 159 **** 100% 40 160 **** 100%  40 161 **** 100%  40 162 *** 40 163 **** 100%  40 164**** 100%  40 165 0 10% 40 166 *** 60% 40 191 0 10% 40 192 0 10% 40201 * 10% 40 202 0 10% 40 206 **** 100%  40 207 **** 100%  40 208 0 20%40 209 *** 90% 40 210 *** 70% 40 211 **** 100%  40 212 0 10% 40 214 ****100%  40 215 0 20% 40 216 **** 100%  40 218 *** 90% 40 219 *** 90% 40220 **** 100%  40 221 **** 100%  40 238 0 10% 10 241 0  0% 10 253 ***80% 10 254 ** 40% 10 255 0  0% 10 256 *** 90% 10 257 **** 100%  10 258*** 100%  10 259 *** 100%  20

Biological Example 4: Mouse Lung Cancer Model

A tumor from xenograft mouse model of lung cancer (LL/2) was grown usingthe methods described herein to establish an ex vivo model of tumorangiogenesis. Treatment did not start until the new tumor endothelialcells had grown for 5 days. After drug treatment was done for two days,cell survival was assessed by a two-color assay using a mixture offluorescein diacetate (green dye) and propidium iodide (red dye). Greencells represented live cells. Red cells represented dead cells. Orangecells represented a mixture of live and dead cells. The percent celldeath is calculated according the ratio of the red area and totalendothelial cell area.

The activity of the tested compounds is provided in Table 4 below.Morphology observations after 48 hours are provided under the column “48hrs,” wherein: “0” indicates all cells have normal endothelial cellmorphology (cells are elongated and connect to neighbor cells); “*”indicates 50% or less of cells vesicularize in cell shape; “**”indicates more than 50% but less than 100% of endothelial cellsvesicularize in cell shape; “***” indicates 100% of endothelial cellsvesicularize in cell shape; “****” indicates 100% of endothelial cellsvesicularize in cell shape and look flattened in morphology (indicatingdisintegration of the cell body). Vesicularization in cell shapeindicates that the endothelial cells no longer have the elongated shapeand no longer connect to neighbor cells.

TABLE 4 Lung LL2 ex vivo model of tumor angiogenesis No 48 hrs Celldeath Conc. (μm) 42 0 30% 40 43 *** 100%  40 44 ** 50% 40 45 ** 10% 4046 **** 100%  40 47 0 50% 40 48 ** 60% 40 49 0 30% 40 50 *** 90% 40 51**** 100%  40 52 ** 50% 40 54 0 50% 40 55 ** 70% 40 56 * 20% 40 57 0 40%40 58 0 50% 40 59 0 40% 40 61 0 50% 40 62 *** 30% 40 63 ** 50% 40 64 ***100%  40 65 0 10% 40 66 0 10% 40 67 0 10% 40 68 *** 80% 40 69 0 20% 4070 *** 40% 40 71 * 10% 40 72 0 20% 40 73 0 10% 40 74 *** 60% 40 75 **80% 40 76 0 20% 40 77 ** 80% 40 78 0 40% 40 79 ** 20% 20 80 *** 100%  2081 0  0% 40 82 0 60% 40 83 0 20% 40 84 ** 100%  40 85 0 80% 40 86 ***100%  20 87 0  0% 40 88 0 70% 40 89 *** 100%  20 90 0 10% 40 91 *** 80%20 92 0 10% 20 93 *** 100%  20 94 0 20% 40 95 0 10% 40 96 0  0% 20 97 **50% 20 98 ** 10% 20 99 0 10% 40 100 **** 100%  40 101 *** 100%  20 102 020% 20 103 0 10% 20 104 0 20% 20 105 0  0% 20 106 0  5% 20 107 0  0% 20108 0  0% 20 109 0  0% 20 110 *** 95% 20 111 0 30% 20 112 *** 70% 20 1130 10% 20 114 0  5% 20 115 0 10% 20 116 *** 100%  20 117 *** 100%  20 118*** 100%  20 119 *** 100%  20 120 0  5% 20 121 ** 50% 40 122 0 10% 20125 * 10% 20 126 0 10% 20 133 ** 10% 20 134 **** 20 141 **** 90% 20 142**** 20 143 0 40% 40 151 **** 100%  40 152 * 20% 20 154 * 30% 40 155 ***80% 40 156 ** 30% 40 157 *** 100%  40 158 **** 100%  40 159 **** 100% 40 160 **** 100%  40 161 **** 90% 40 162 *** 70% 40 163 **** 95% 40 164**** 95% 40 165 * 10% 40 166 0 10% 40 167 0 40% 20 168 0 10% 20 169 040% 20 170 0 10% 20 171 0 40% 40 172 **** 100%  40 173 ** 50% 40 174 030% 40 175 0 30% 40 176 *** 100%  40 177 **** 100%  40 178 **** 100%  40179 *** 60% 10 180 *** 70% 10 181 **** 100%  40 182 **** 100%  40 183**** 100%  10 184 0  5% 10 185 * 30% 10 186 **** 90% 10 187 0 30% 40 1910 30% 40 192 *** 60% 40 193 0 30% 40 195 0 40 196 0 30% 40 197 0 20% 40198 0 30% 40 199 0 30% 40 200 0 30% 40 201 0 30% 40 202 ** 30% 40 206 030% 20 207 ** 20 208 0 50% 40 209 * 60% 40 210 0 50% 40 211 **** 100% 40 212 0 50% 40 213 0 30% 40 214 **** 100%  40 215 0 30% 40 216 ****100%  40 217 0 30% 40 218 **** 100%  40 219 **** 60% 40 220 **** 100% 40 221 **** 100%  40 223 *** 30% 40 (rim) 225 0 40% 40 226 * 10% 40 2270 10% 40 228 0  5% 40 229 0 30% 40 230 *** 100%  40 231 *** 100%  40 2320 10% 40 233 0  5% 40 234 *** 100%  40 235 0 10% 40 236 0  5% 40 237 ***100%  40 238 *** 100%  40 239 0 40% 40 240 0 30% 40 241 0 40% 40 242 030% 40 243 0 20% 40 244 0 20% 40 245 0 40% 40 246 *** 95% 20 247 *** 60%20 248 * 60% 20 249 *** 60% 20 250 *** 90% 20 251 *** 60% 20 253 ****100%  20 254 *** 100%  20 255 * 10% 20 256 **** 100%  20 257 **** 100% 20 258 **** 100%  20 259 *** 95% 20 262 0 20% 10 263 **** 100%  10 264 *20% 10 265 * 20% 10 266 0  5% 10 267 0  5% 10 268 *** 50% 20 269 ****100%  20 270 * 50% 20 271 *** 60% 20 272 * 20% 20 273 *** 60% 20 274 010% 20 275 0  5% 20 276 *** 100%  20 277 ** 60% 10 278 * 50% 10 279 ****100%  20 280 *** 100%  20 281 ** 50% 20 282 0 10% 10 283 0  5% 10 284 010% 10 285 *** 60% 10 286 0  0% 20 (24 hrs) (24 hrs) 287 * 40% 20 (24hrs) (24 hrs) 288 *** 50% 10 289 ** 20% 20 290 *** 50% 10 291 * 10% 20(24 hrs) (24 hrs) 292 * 10% 20 (24 hrs) (24 hrs) 294 * 50% 40 296 0 20%40 300 0 20% 40 302 0 70% 40 306 0 40% 40 308 0 20% 40 310 0 10% 40 3110 30% 40 312 **** 100%  40 317 0 30% 40 318 0 30% 40 320 0 30% 40 321 040% 40 322 0 30% 40 323 0 30% 40 324 0 60% 40 325 * 30% 40 326 0 30% 40327 0 20% 40 328 0 30% 40 329 *** 40% 40 330 *** 50% 40 331 0 10% 40 3320  0% 40 333 0  0% 40 336 0  0% 40 339 ** 50% 20 340 *** 60% 20 341 ***80% 20 342 *** 60% 20 343 *** 50% 20 344 * 10% 20 345 *** 50% 20 346 *20% 20 347 *** 30% 20 348 * 20% 20 350 0 20% 40 351 *** 100%  40 352 ***100%  40 353 0  0% 40 354 0  0% 40 355 0  0% 40 356 0  0% 40 357 0  0%40 358 0  0% 40 359 0 20% 40 360 0 20% 40 362 *** 20% 20 363 *** 30% 20364 *** 30% 20 365 *** 20% 20 366 0 10% 20 367 0  5% 20 368 ** 20% 20369 * 20% 20 370 ** 20% 20 371 *** 30% 20 372 ** 20% 20 373 * 20% 20 374** 20% 20 375 * 50% 20 376 0 10% 20 377 0 10% 20 378 *** 30% 20

Certain other compounds described herein also showed activity in causingendothelial cell death in other angiogenesis assays.

Biological Example 5: Ex Vivo Primary Tumor (Colon Cancer) AngiogenesisModel

CT26.CL25 cell line was purchased from ATCC. Frozen vials were thawedand expanded in vitro. Once the cell number reached 6.25 million, tumorcells were inoculated into Balb/c mice.

Tumor-bearing mice were randomized into three (3) groups of up to 10animals per group when mean tumor volume reached approximately 250-500mm³. Treatment (single or multiple doses) with test compounds andvehicle was started on the day of randomization. Test compounds orvehicle were formulated with recombinant human serum albumin, oxalicacid and saline as described herein. The test composition or vehicle wasadministered using an insulin syringe over 10 seconds within 5 minutesof preparing the dosing solution.

All tumor-bearing mice were observed daily for up to 10-days post dosingwith photos taken on DO (dose administration), Dl, D3, D5, D7, D8, D10(where D8 and D10 are optional and dependent on study end date). On thefinal study day, mice were euthanized, whole mouse photos with shavedtumors facing up were taken of tumor-bearing mice, and the tumors wereremoved and cut in half. Tumors along with 1 mm of adjacent tissue fromall animals in the study were collected for histopathology.

Tumor cell preparation: Cryogenic vials containing CT26.CL25 cellsreceived from ATCC were cultured using a protocol comprising DMEM(Gibco, #11995-065); 10% FBS (VWR, #97068-085); and 1× Pen/Strep (Gibco,#15140-122).

Procedure: On the day of injection, cells were washed in serum-freemedia, counted and resuspended in cold serum-free media at aconcentration of one million (1M) cells per 100 μL. Cells were preparedfor injection by withdrawing 100 μL of cell suspension into a 1 mLsyringe. The cell suspension and filled syringes were kept on ice.

Mice were prepared for injection using standard approved anesthesia.

Fur Removal: Mice fur was removed using Veet fast acting hair removalgel cream. A thin layer of hair removal cream was applied on the rightrear flank area of the mouse. After 30-60 seconds, the cream and furwere wiped away, and wiped once more with water or alcohol if necessary.

One mouse at a time was immobilized and the site of injection wasdisinfected with an alcohol swab. 100 μL of the cell suspension wassubcutaneously injected into the right rear flank of the mouse. Duringimplantation, a new syringe and needle was used for every mouseinoculated. The cells were drawn up into a 1 mL syringe (no needleattached) to a volume of 150 μL, with the 50 μL nearest to the plungerbeing air and 100 μL of cell suspension. Once the cells were drawn upthe needle was attached (without priming the needle). For implant, theskin was lifted or tented using forceps to ensure a subcutaneousinjection. The cells were injected, and each mouse was tagged.

Tumor Measurement: The mice were monitored every other day for palpabletumors, or any changes in appearance or behavior and for mice showingany signs of morbidity or mortality. Once tumors were palpable, tumorswere measured daily using calipers. Tumor volume was calculated usingthe following equation: (longest diameter*shortest diameter2)/2.

Once tumors were of the appropriate size (˜250-500 mm3) to begin thestudy, tumors and body weights were measured daily for 7-10 dayspost-treatment.

Randomization: When average tumor volume reached approximately 250-500mm³, mice were randomly assigned to treatment groups with up to 10animals per group. All treatment groups were dosed within 24 hours ofrandomization according to the protocol shown in the Table below.

Dose Frequency Dose Volume Group Treatment N Dose Route & Duration DoseLevel (μL) 1 Test 10 Bolus 2 injections; 5 mM 280 μL compound Injection2 hours (2.5 mM/injection) (140 μL/injection) (administered apart in 10seconds) 2 Vehicle 10 Bolus 2 injections; 5 mM 280 μL Injection 2 hours(2.5 mM/injection) (140 μL/injection) (administered apart in 10 seconds)

Tumor size measurements were taken from Day 0 through Day 7. Mice werephotographed every other day starting from Day 0. Body weight wasmeasured daily following randomization and treatment. If body weightloss of >10% was observed, DietGel was given ad libitum. If body weightloss of >20% was observed, the animal was monitored daily for signs ofrecovery for up to 72 hours. If there were no signs of recovery, theanimal was sacrificed for humane reasons as per IACUC protocolregulations.

FIG. 3A-B shows tumor shrinkage and necrosis when mice were treated withcertain compounds described herein. FIG. 3A shows that 3 days afterinjection, all the tumors were shrinking FIG. 3B shows that the tumorshrinkage was maintained 6 days after injection.

Biological Example 6. Preferential Binding to PLXDC1

This example shows that compounds of the disclosure bind to theextracellular domain of PLXDC.

The high affinity interaction between compound 346 (Table 3) and theextracellular domain of PLXDC1 (PLXDC1-ECD). Compound 346 suppressed theendogenous tryptophan fluorescence of PLXDC1-ECD in a dose-dependentmanner (FIG. 4A-B). FIG. 4A presents raw data of the tryptophanfluorescence of PLXDC1-ECD as measured in a fluorometer after addingdifferent concentrations of the compound, and FIG. 4B shows thedose-dependent curve of the suppression of tryptophan fluorescence.Tryptophan fluorescence without the compound added is defined as 1. Theestimated Kd value is 50 nM.

Biological Example 7. Killing of Tumor Endothelial Cells byPLXDC-Activating Compounds

This example investigates the mechanism by which the compounds killtumor endothelial cells, and demonstrates their killing activities.

Through RNAseq analysis of PLXDC1-expressing endothelial cells killingby PLXDC1-activating compounds, this example identified atranscriptional factor called Gfi1b that specifically induced duringPLXDC1-mediated cell killing By linking its promotor to a luciferasereporter gene, this example developed a PLXDC1 receptor activationassay. PLXDC1-activating compounds 346 and 342 (Table 3, labeled asA-Compound-1 and A-Compound-2, respectively) highly activated thepromotor activity in PLXDC1-expressing cells, but not in cells withoutPLXDC1 (FIG. 5A). Likewise, these compounds activated the promotoractivity in PLXDC2-expressing cells, but not in cells without PLXDC2(FIG. 5B).

FIG. 5 therefore shows that the compounds activated both PLXDC1 andPLXDC2 and that they preferentially activate PLXDC1 over PLXDC2. One ofthe compounds, A-Com-2, strongly differentiates between the tworeceptors. As a control, Fluorouracil, a chemotherapy agent that killsdividing cells by apoptosis does not activate this promoter. This datademonstrates that the cell death mediated by PLXDC1 activation isdifferent from chemotherapy agent-triggered apoptosis.

The killing of human PLXDC1-expressing endothelial cells by thecompounds is visualized in FIG. 6. The top three pictures representcontrol cells and the lower three pictures represent compound-treatedcells, showing light microscopy picture (FIG. 6A, left), live cell(middle) and dead cell staining (right). Live cells were stained usingFluorescein diacetate (green signal) and dead cells were stained usingpropidium iodide (red signal). Quantitation of the killing of humanPLXDC1-expressing endothelial cells by the compounds and two antibodiesare shown in FIG. 6B. Incubation time of the compounds and antibodieswas 24 hours.

Biological Example 8. Specific Killing of Pathogenic Blood Vessels inIschemia-Induced Retinopathy/Tumor

This example examines the expression of the PLXDC proteins on pathogenicblood vessels and normal healthy blood vessels, in different diseases,and confirms that the compounds of the instant disclosure specificallykill the pathogenic blood vessels.

The expression of PLXDC1 in pathogenic blood vessels of ischemia-inducedretinopathy was examined and shown in FIG. 1, which shows that PLXDC1was not expressed in healthy blood vessels. It was then demonstratedthat the compounds (e.g., compounds 346) specifically suppressedpathogenic blood vessels in vivo without affecting healthy blood vesselsin ischemia-induced retinopathy (FIG. 7). FIG. 7A includes a schematicdiagram of the experimental design for ischemia-induced retinopathy. Thehigh oxygen environment caused blood vessel loss (vaso-obliteration). Inroom air, loss of vessels triggered abnormal angiogenesis that generatedpathogenic blood vessels on the top of the retina (marked in yellow inFIG. 7D). Treatment was applied during the return to room air bysubcutaneous injection. The lower graph in FIG. 7A shows quantitation ofhealthy blood vessels, vaso-obliteration and pathogenic blood vesselsbetween the control (n=10) and treated retinas (n=10).

Treatment by PLXDC1-activating compound (compound 346/A-Compound-1)highly suppressed pathogenic blood vessels (two asterisks) whileimproving the amount of healthy blood vessels (one asterisk). FIG. 7Bincludes representative images of flat-mounted control retinas (uppertwo images) and retinas from compound treated mice (lower two images).The same retinas in B with vaso-obliteration areas marked in white color(FIG. 7C). These images illustrate that compound-treated retinas wentthrough vaso-obliteration like the control retinas. The same retinas inB with pathogenic blood vessels marked in yellow color (FIG. 7D). Theseimages illustrate that compound-treated retinas have highly decreasedpathogenic blood vessels as compared to the control retinas.

The killing activity was further demonstrated with tumor samples invivo. Treatment was done at day 0 by bolus IV injection of compound 346in a tumor animal model. FIG. 8A charts raw data of tumor growth curvesof the mice in the control group. FIG. 8B presents raw data of tumorgrowth curves of the mice in the treatment group. FIG. 8C compares thecombined growth data of the control group and the treatment group.Unlike in the control group, compound 346 shrank the tumorssignificantly.

Tumor morphological changes on live animals due to the treatment byPLXDC1-activating compound were examined Pictures of the whole animalsin the experiment described in FIG. 9 show tumor morphological and colorchanges on day 1 and day 3 (FIG. 9). Tumors in the treatment groupsbecomes darker in color on day 1 due to the destruction of tumor bloodvessels and accumulation of blood in the tumors. Tumors in the treatmentgroups started to become yellower in color on day 3, consistent with theonset of tumor necrosis due to the lack of tumor blood vessels.

FIG. 10 presents pictures of the whole animals showing tumormorphological and color changes on day 7. tumors in the control grouphave grown to large sizes, tumors in the treatment groups have highlyshrunk in size and become yellow in color.

FIG. 11 shows morphological changes of dissected tumors due to thetreatment by the compound. Pictures of the dissected tumors showed tumormorphological and color changes on day 7. While the tumors in thecontrol group are reddish in color, tumors in the treatment groups hadhighly shrunk in size and become yellow in color, consistent with thelack of tumor blood vessels and tumor necrosis. These data, therefore,demonstrate that the PLXDC1-activating compounds can kill tumor bloodvessels in vivo to cause strong tumor necrosis and shrinkage.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this disclosure belongs.

The disclosures illustratively described herein may suitably bepracticed in the absence of any element or elements, limitation orlimitations, not specifically disclosed herein. Thus, for example, theterms “comprising”, “including,” “containing”, etc. shall be readexpansively and without limitation. Additionally, the terms andexpressions employed herein have been used as terms of description andnot of limitation, and there is no intention in the use of such termsand expressions of excluding any equivalents of the features shown anddescribed or portions thereof, but it is recognized that variousmodifications are possible within the scope of the claims.

All publications, patent applications, patents, and other referencesmentioned herein are expressly incorporated by reference in theirentirety, to the same extent as if each were incorporated by referenceindividually. In case of conflict, the present specification, includingdefinitions, will control.

It is to be understood that while the disclosure has been described inconjunction with the above embodiments, that the foregoing descriptionand examples are intended to illustrate and not limit the scope of thedisclosure. Other aspects, advantages and modifications within the scopeof the disclosure will be apparent to those skilled in the art to whichthe disclosure pertains.

1. A method for treating a pathogenic blood vessel-related disorder in asubject in need thereof, comprising administering to the subject aneffective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof; wherein nis 0, 1, 2, 3 or 4; R¹ is selected from optionally substituted amino,optionally substituted aryl, optionally substituted cycloalkyl,optionally substituted heterocyclyl, and optionally substitutedheteroaryl; R² is selected from H, halo, alkyl, alkenyl, alkynyl, —OH,alkoxy, alkenoxy, alkynoxy, —CN, —NO₂, alkylthio, sulfoxido, sulfonyl,and amino; R⁵, R⁷ and R⁸ are each independently selected from H, halo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, alkylthio, sulfoxido,sulfonyl, carboxy, ester, —CN, —NO₂, amino, and amido; R⁶ is selectedfrom H, halo, alkyl, hydroxy, alkoxy, alkylthio, sulfoxido, sulfonyl,carboxy, ester, —CN, —NO₂, amino, amido, sulfinamido, sulfonamido,optionally substituted heterocyclyl, optionally substituted heteroaryl,poly(ethylene glycol), and methoxypoly(ethylene glycol), or R⁶ and R⁷together with atoms to which they are attached form a optionallysubstituted cycloalkyl, optionally substituted heterocyclyl, optionallysubstituted aryl, or optionally substituted heteroaryl; and each R⁹ isindependently selected from halo, alkyl, —OH, alkoxy, —CN, and amino.2.-12. (canceled)
 13. A compound of Formula (I):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof; wherein nis 0, 1, 2, 3 or 4; R¹ is selected from amino, optionally substitutedheterocyclyl, and optionally substituted heteroaryl; R² is selected fromH, halo, alkyl, alkenyl, alkynyl, —OH, alkoxy, —CN, —NO₂, alkylthio,sulfoxido, sulfonyl, and amino; R⁵, R⁷ and R⁸ are each independentlyselected from H, halo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy,alkylthio, sulfoxido, sulfonyl, carboxy, ester, —CN, —NO₂, amino, andamido; R⁶ is selected from H, halo, alkyl, hydroxy, alkoxy, alkylthio,sulfoxido, sulfonyl, carboxy, ester, —CN, —NO₂, amino, amido,sulfinamido, sulfonamido, heterocyclyl, heteroaryl, poly(ethyleneglycol), and methoxypoly(ethylene glycol), or R⁶ and IV together withatoms to which they are attached form a cycloalkyl, heterocyclyl, aryl,or heteroaryl; and each R⁹ is independently selected from halo, alkyl,—OH, alkoxy, —CN, and amino; wherein the compound has at least one ofthe following: 1) R² is selected from C₂₋₃₀alkyl, —OH, C₁₋₄₀alkoxy,C₁₋₄₀alkenoxy, C₁₋₄₀alkynoxy, —NO₂, alkylthio, sulfoxido, sulfonyl, andamino, where a) when R² is ethyl, then R⁶ is not methyl or methoxy,and/or b) when R² is methoxy, then R⁶ is not halo, C₁₋₂ alkyl or C₁₋₂alkoxy; 2) R¹ is optionally substituted heteroaryl, optionallysubstituted bridged heterocyclyl, optionally substituted fusedheterocyclyl, or optionally substituted cycloheptyl; 3) R¹ isheterocyclyl substituted with one halo, amino, hydroxy, alkoxy, —CN,—NO₂, alkyl, carboxy, alkylthio, sulfoxido, sulfonyl, sulfinamido,sulfonamido, optionally substituted cycloalkyl, optionally substitutedheterocyclyl, optionally substituted heteroaryl, poly(ethylene glycol),or methoxypoly(ethylene glycol), where if the substituent is alkyl, thealkyl is further substituted with one substituent selected from halo,amino, alkoxy, —CN, —NO₂, carboxy, ester, alkylthio, sulfoxido,sulfonyl, sulfinamido, sulfonamido, cycloalkyl, heterocyclyl,poly(ethylene glycol), methoxypoly(ethylene glycol), pyrrolidinyl andpiperidinyl; or the alkyl is substituted with at least one —OR³¹,wherein R³¹ is poly(ethylene glycol) or methoxypoly(ethylene glycol); 4)R¹ is amino substituted with at least one substituent selected fromalkyl, cycloalkyl, heterocyclyl, heteroaryl, poly(ethylene glycol) ormethoxypoly(ethylene glycol) and amino, where the alkyl is substitutedwith at least one substituent selected from halo, amino, hydroxy,alkoxy, —CN, —NO₂, amido, carboxy, ester, alkylthio, sulfoxido,sulfonyl, sulfinamido, sulfonamido, cycloalkyl, heterocyclyl, andheteroaryl; or 5) R⁶ is alkyl substituted with at least one substituentselected from halo, amino, hydroxy, alkoxy, cycloalkoxy,heterocycloalkoxy, aryloxy, heteroaryloxy, poly(ethylene glycol)-oxy,methoxypoly(ethylene glycol)-oxy, —CN, —NO₂, oxo, amido, carboxy, ester,alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido, heterocyclyl,cycloalkyl, aryl, heteroaryl, poly(ethylene glycol) andmethoxypoly(ethylene glycol).
 14. The compound of claim 13, wherein n is0, 1 or
 2. 15. The compound of claim 13, wherein when R² is C₁₋₆ alkyl,R⁶ is not C₁₋₆ alkyl or C₁₋₆ alkoxy.
 16. The compound of claim 13,wherein R¹ is an optionally substituted heterocyclyl, such as anoptionally substituted 5- to 9-membered heterocyclyl, an optionallysubstituted 5- to 7-membered heterocyclyl, or an optionally substituted5- to 6-membered heterocyclyl.
 17. The compound of claim 13, wherein R¹is an optionally substituted heteroaryl, such as an optionallysubstituted 5- or 6-membered heteroaryl.
 18. The compound of claim 13,wherein R¹ is heterocyclyl substituted with at least one substituentselected from oxo, —OH, —OR²⁸, —N(R²⁸)₂, alkyl, aryl, and heterocyclyl,the alkyl is substituted with at least one substituent selected from—N(R³¹)₂, —S(O)₀₋₂NR³¹R³¹, —C(O)N(R³¹)₂, heterocyclyl, cycloalkyl,pyrrolidinyl and piperidinyl; or the alkyl is substituted with at leastone —OR^(31a), wherein R^(31a) is poly(ethylene glycol) ormethoxypoly(ethylene glycol); and each R²⁸ and R³¹ are independently Hor alkyl.
 19. The compound of claim 13, wherein R¹ is heteroaryl orheterocyclyl substituted with a second heterocyclyl; and the secondheterocyclyl is unsubstituted or substituted with one or moresubstituents selected from —OH, —C(O)Oalkyl, —C(O)NHalkyl, alkyl, aryl,and heterocyclyl; and wherein the alkyl and heterocyclyl are eachunsubstituted or substituted with one or more substituents selected from—OH, alkyl and aryl.
 20. The compound of claim 13, wherein R¹ is

wherein each s and t is independently 0, 1, 2 or 3, provided that thesum of s and t is 1, 2, 3, or 4; R²⁰ is selected from alkyl, cycloalkyl,heterocyclyl, aryl, and heteroaryl; and R^(20a) is H, NH₂, or OH. 21.The compound of claim 13, wherein R¹ is heterocyclyl, optionallysubstituted with a sugar moiety.
 22. The compound of claim 13, whereinR¹ is —NR³R⁴, and R³ is H or alkyl that is unsubstituted or substitutedwith at least one substituent selected from —OH, —N(R²⁸)₂, andheteroaryl, and R⁴ and R²⁸ are each independently H or alkyl.
 23. Thecompound of claim 13, wherein R¹ is selected from


24. The compound of claim 13, wherein R¹ is selected from


25. The compound of claim 13, wherein R¹ is selected from


26. The compound of claim 13, wherein R¹ is selected from


27. The compound of claim 13, wherein R¹ is selected from


28. The compound of claim 13, wherein R² is selected from C₁₋₆ alkyl,—NO₂, —OR¹⁸, and CN, and R¹⁸ is selected from C₁₋₁₆ alkyl, C₁₋₆haloalkyl, and C₁₋₆ aminoalkyl.
 29. (canceled)
 30. The compound of claim28, wherein R² is —O(CH₂)_(m)CH₃, wherein m is an integer selected from1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 12, 13, 14, 15, and
 16. 31. Thecompound of claim 13, wherein R² is amino, substituted with one or moresubstituents selected from alkyl, cycloalkyl, heterocyclyl, aryl,heteroaryl, and amino.
 32. (canceled)
 33. The compound of claim 31,wherein the amino substituent is alkyl substituted with at least onesubstituent selected from —C(O)OH, —OH, phenyl and pyridyl, and thephenyl and pyridyl are each independently unsubstituted or substitutedwith halo, alkyl or —OH.
 34. The compound of claim 13, wherein R⁶ isselected from halo, alkyl, —OR^(31a), —S(O)₀₋₂R¹⁶, —C(O)OR¹⁵, —NO₂, and—C(O)NR¹⁵R¹⁵; R¹⁵ is selected from H, methyl, ethyl, iPr, —CH₂CH₂NEt₂,and —CH₂CH₂OH; R¹⁶ is methyl; and R¹⁷ is selected from methyl,trifluoromethyl and butyl. 35.-40. (canceled)
 41. The compound of claim13, wherein R⁶ is selected from


42. The compound of claim 13, wherein R⁵, R⁷ and R⁸ are each H.
 43. Thecompound of claim 13, wherein n is 1 or 2 and each R⁹ is independentlyhalo.
 44. The compound of claim 13, wherein the compound is of Formula(II):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof.
 45. Thecompound of claim 13, wherein the compound is of Formula (III):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof.
 46. Thecompound of claim 13, wherein the compound is of Formula (IV):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof.
 47. Thecompound of claim 13, wherein the compound is of Formula (V):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof, whereineach of s, t, u, and v is independently 0, 1, 2, or 3, provided that thesum of s and t is 1, 2, 3 or 4, and the sum of u and v is 1, 2, 3 or 4;w is 0, 1, 2, or 3; Z¹ is C or N, when Z¹ is C, R^(20a) is selected fromH, halo, oxo, —NH₂, —OH, —CN, —NO₂, —NHR²⁸, —N(R²⁸)₂, —C(O)R²⁸,—C(O)OR²⁸, —C(O)OH, —OC(O)R²⁸, —S(O)₀₋₂R²⁸, —NHS(O)₀₋₂R²⁸,—S(O)₀₋₂NHR²⁸, —NHS(O)₀₋₂NHR²⁸, —C(O)NH₂, —C(O)NHR²⁸, —C(O)N(R²⁸)₂,—NHC(O)R²⁸, —OC(O)NHR²⁸, —NHC(O)OR²⁸, —OC(O)N(R²⁸)₂, —NR³²C(O)NH₂,—NR³²C(O)NHR²⁸, —NR³²C(O)N(R²⁸)₂, poly(ethylene glycol),methoxypoly(ethylene glycol), C₁₋₃₀ alkyl optionally substituted with OHor —C(O)OH, and C₁₋₃₀ heteroalkyl optionally substituted with OH or—C(O)OH, wherein R³² is H or C₁₋₄ alkyl, and R²⁸ is C₁₋₄ alkyl; when Z¹is N, R^(20a) is absent; Z² is C or N; Z³ is CH₂, CHR²⁵, CR²⁵R²⁵, orNR²⁵, O, or S(O)₀₋₂ and R²⁵ is selected from H and alkyl; and each of n,R², R⁵, R⁶, R⁷, R⁸, and R⁹ are as defined in claim
 1. 48. A compound ofFormula (XII):

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof; wherein: R¹is optionally substituted

each of s, t, u, v, p and q is independently 0, 1, 2, or 3, providedthat the sum of s and t is 1, 2, 3 or 4, the sum of u and v is 1, 2, 3or 4, and the sum of p and q is 1, 2, 3 or 4; y is 0 or 1; z is 0 or 1;provided that y and z are not both 0; Z¹ is C or N; when Z¹ is C,R^(20a) is H, halo, hydroxy, alkyl, or hydroxyalkyl; when Z¹ is N,R^(20a) is absent; Z² is CH or N; Z³ is C or N; when Z³ is C, R^(20b) isH, halo, hydroxy, alkyl, or hydroxyalkyl; when Z³ is N, R^(20b) isabsent; Z⁴ is CH or N; Z⁵ is CH₂, CHR²⁵, CR²⁵R²⁵, C(═O), NR²⁵, O, orS(O)₀₋₂; each R²⁵ is independently H, halo, alkyl or hydroxyalkyl; R²¹¹is C₂₋₄₀ alkyl, C₂₋₄₀ alkenyl, or C₂₋₄₀ alkynyl; R⁶ is H, halo, alkyl,haloalkyl, hydroxy, alkoxy, haloalkoxy, alkylthio, sulfoxido, sulfonyl,carboxy, ester, —CN, —NO₂, amino, amido, sulfinamido, or sulfonamido;and R⁹¹ and R⁹² are independently selected from H and halo.
 49. Thecompound of claim 48, wherein R²¹¹ is C₅₋₃₀ alkyl.
 50. The compound ofclaim 48, wherein R²¹¹ is C₁₀₋₂₅ alkyl.
 51. The compound of claim 48,wherein R⁹¹ and R⁹² are independently selected from H and F.
 52. Thecompound of claim 48, wherein R⁶ is hydroxy, alkoxy, haloalkoxy,alkylthio, sulfoxido, or sulfonyl. 53.-54. (canceled)
 55. The compoundof claim 48, wherein each heterocyclyl in R¹ is independently andoptionally further substituted with halo, hydroxy, alkyl, hydroxyalkyl,or oxo.
 56. The compound of claim 48, wherein R¹ is selected from


57. The compound of claim 48, wherein R¹ is selected from


58. The compound of claim 48, wherein the compound is selected from

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof.
 59. Acompound selected from the group consisting of 1

3-((4-ethylphenyl)sulfonyl)-4-(4-methylpiperazin-1-yl)-6-(trifluoromethoxy)quinoline 2

3-((4-ethylphenyl)sulfonyl)-4-(piperidin-1-yl)-6-(trifluoromethoxy)quinoline 3

4-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)morpholine 4

3-((4-ethylphenyl)sulfonyl)-4-(4-methylpiperidin-1-yl)-6-(trifluoromethoxy)quinoline 5

2-(4-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperazin-1-yl)ethan-1-ol 6

3-((4-ethylphenyl)sulfonyl)-4-(4-ethylpiperazin-1-yl)-6-(trifluoromethoxy)quinoline 7

3-((4-ethylphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(trifluoromethoxy)quinoline 8

1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 9

ethyl 4-(3-((4-ethylphenyl)sulfonyl-6-(trifluoromethoxy)quinolin-4-yl)piperazine-1-carboxylate 10

3-((4-ethylphenyl)sulfonyl)-4-(4-(4-fluorophenyl)piperazin-1-yl)-6-(trifluoromethoxy)quinoline 11

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 12

1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-4-phenylpiperidin-4-ol 13

3-((4-ethylphenyl)sulfonyl)-4-(4-phenylpiperazin-1-yl)-6-(trifluoromethoxy)quinoline 14

3-((4-ethylphenyl)sulfonyl)-4-(pyrrolidin-1-yl)-6-(trifluoromethoxy)quinoline 15

1-(3-((4-ethylphenyl)sulfonyl)-6-methoxyquinolin-4-yl) piperidin-4-ol 16

ethyl 4-(3-((4-ethylphenyl)sulfonyl)-6-methoxyquinolin-4-yl)piperazine-1-carboxylate 17

3-((4-ethylphenyl)sulfonyl)-4-(4-(4-fluorophenyl)piperazin-1-yl)-6-methoxyquinoline 18

N-cyclohexyl-3-((4-ethylphenyl)sulfonyl)-6-methoxyquinolin-4- amine 19

3-((4-ethylphenyl)sulfonyl)-N-(4-fluorophenyl)-6-methoxyquinolin-4-amine 20

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(4-methylpiperazin-1-yl)quinoline 21

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(piperidin-1- yl)quinoline 22

4-(3-((4-ethylphenyl)sulfonyl)-6-methoxyquinolin-4-yl)morpholine 23

3-((4-ethylphenyl)sulfonyl-6-methoxy-4-(4-methylpiperidin-1-yl)quinoline 24

3-((4-ethylphenyl)sulfonyl)-4-(4-ethylpiperazin-1-yl)-6-methoxyquinoline 25

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(pyrrolidin-1-yl)quinoline 26

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(4-phenylpiperazin-1-yl)quinoline 27

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)-6-methoxyquinoline28

1-(3-((4-ethylphenyl)sulfonyl)-6-methoxyquinolin-4-yl-4-phenylpiperidin-4-ol 29

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(4-methyl-1,4-diazepan-1-yl)quinoline 30

3-((4-ethylphenyl)sulfonyl-4-(4-isopropylpiperazin-1-yl)-6-methoxyquinoline 31

4-(azepan-1-yl)-3-((4-ethylphenyl)sulfonyl)-6-methoxyquinoline 32

3-((4-ethylphenyl)sulfonyl)-6-methyl-4-(4-methylpiperazin-1-yl)quinoline33

3-((4-ethylphenyl)sulfonyl)-6-methyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline 34

1-(3-((4-ethylphenyl)sulfonyl)-6-methylquinolin-4-yl)piperidin-4-ol 35

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)-6-methyl)quinoline 36

3-((4-ethylphenyl)sulfonyl)-6-methyl-4-(piperidin-1-yl) quinoline 37

3-((4-ethylphenyl)sulfonyl)-6-fluoro-4-(4-methylpiperazin-1-yl)quinoline 38

3-((4-ethylphenyl)sulfonyl)-6-fluoro-4-(4-methyl-1,4-diazepan-1-yl)quinoline 39

1-(3-((4-ethylphenyl)sulfonyl)-6-fluoroquinolin-4-yl)piperidin-4-ol 40

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)-6-fluoroquinoline 41

3-((4-ethylphenyl)sulfonyl-6-fluoro-4-(piperidin-1-yl)quinoline 42

2-(4-(3-((4-ethylphenyl)sulfonyl-6-(trifluoromethoxy)quinolin-4-yl)-1,4-diazepan-1-yl)acetic acid 43

4-([1,4′-bipiperidin]-1yl)-3-((4-methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 44

1-(3-((4-methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 45

4-(4-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperazin-1-yl)benzonitrile 46

3-((4-ethylphenyl)sulfonyl)-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 47

ethyl)-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidine-4-carboxylate 48

(1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-yl)methanol 49

N-benzyl-3-((4-ethylphenyl)sulfonyl)-N-methyl-6-(trifluoromethoxy)quinolin-4-amine 50

3-((4-ethylphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 51

3-((4-ethylphenyl)sulfonyl-4-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethoxy)quinoline 52

8-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-1,4-dioxa-8-azaspiro[4,5]decane 53

1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidine-4-carboxylate acid 54

4-((4-([1,4′-bipiperidin]-1′-yl)-6-(trifluoromethoxy)quinolin-3-yl)sulfonyl)benzonitrile 55

2-(4-([1,4′-bipiperidin]-1′-yl-3-((4-ethylphenyl)sulfonyl)quinolin-6-yl)acetonitrile 56

4-([1,4′-bipiperidin]-1′-yl)-3-((3,4-dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 57

3-((3,4-dimethoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(trifluoromethoxy)quinoline58

1-(3-((3,4-dimethoxyphenyl)sulfonyl)-6(trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 59

4-([1,4,-bipiperidin]-1′-yl-3-((4-nitrophenyl)sulfonyl-6-(trifluoromethoxy)quinoline 60

4-(4-methyl-1,4-diaxepan-1-yl)-3-((4-nitrophenyl)sulfonyl-6-(trifluoromethoxy)quinoline 61

1-(3-((4-nitrophenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 62

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4-hydroxypiperidin-1-yl)quinoline-6-carboxylate 63

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxylate 64

ethyl 4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6-carboxylate 65

3-((4-ethylphenyl)sulfonyl)-4-(4-hydroxypiperidin-1-yl)quinoline-6-carboxylate acid 66

3-((4-ethylphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxylateacid 67

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6-carboxylate acid 68

3-((3,4-dimethoxyphenyl)sulfonyl)-N,N-diethyl)l-6-trifluoromethoxy)quinolin-4-amine 69

2-((3-((3,4-dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)amino)ethan-1-ol 70

1-(3-((3,4-dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-3-ol 71

3-((3,4-dimethoxyphenyl)sulfonyl)-N,N-dipropyl-6-(trifluoromethoxy)quinolin-4-amine 72

2,2′-((3-((3,4-dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)azanediyl)bis(ethan-1-ol) 73

2-((3-((3,4-dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)amino)ethan-1-ol 74

N,N-dibutyl-3-((3,4-dimethoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-amine75

1-(3-((4-ethylphenyl)sulfonyl)-6-nitroquinolin-4-yl)piperidin-4-ol 76

3-((4-ethylphenyl)sulfonyl-4-(4-methyl-1,4-diazepan-1-yl)-6-nitroquinoline 77

4-([1,4′-bipiperidin]-1′-yl)-3-((4-ethylphenyl)sulfonyl)-6-nitroquinoline 78

N,N-diethyl)l-3-((4-ethylphenyl)sulfonyl)-6-nitroquinolin- 4-amine 79

3-((4-ethylphenyl)sulfonyl)-6-methoxy-4-(1H-1,2,4-triazol-1-yl)quinoline 80

ethyl3-((4-ethylphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinoline-6-carboxylate81

N,N-diethyl)l-3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-amine 82

1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-3-ol 83

3-((4-ethylphenyl)sulfonyl)-6-methoxy-N-(4-methylpiperazin-1-yl)quinolin-4-amine 84

ethyl 3-((4-ethylphenyl)sulfonyl)-4-((4-methylpiperazin-1-yl)amino)quinoline-6-carboxylate 85

3-((4-methoxyphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 86

3-((4-methoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethoxy)quinoline 87

N,N-dibutyl-3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-amine 88

3-((3,4-dimethoxyphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 89

3-((3,4-dimethoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethoxy)quinoline 90

N-(4-methylpiperazin-1-yl)-6-(trifluoromethoxy)-3-((4-(trifluoromethoxy)phenyl)sulfonyl)quinolin-4-amine 91

4-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethoxy)-3-((4-(trifluoromethoxy)phenyl)sulfonyl)quinoline 92

3-((4-butoxyphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 93

3-((4-butoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)-6-(trifluoromethoxy)quinoline 94

3-((4-methoxyphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-nitroquinolin-4-amine 95

2-((3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)amino)ethan-1-ol 96

3-((3,4-dimethoxyphenyl)sulfonyl)-6,7-dimethoxy-4-(1H-1,2,4-triazol-1-yl)quinoline 97

3-((4-methoxyphenyl)sulfonyl)-6-nitro-4-(1H-1,2,4-triazol-1-yl)quinoline 98

2-(3-((4-methoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinolin-6-yl)acetonitrile99

2-(3-((4-methoxyphenyl)sulfonyl)-4-((4-methylpiperazin-1-yl)amino)quinolin-6-yl)acetonitrile100

N,N-diethyl)l-2-(4-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-1,4-diazepan-1-yl)ethan-1-amine 101

N,N-diethyl)l-2-((1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-yl)oxy)ethan-1-amine 102

1′-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl-[1,4′-bipiperidin]-4-ol 103

N,N-diethyl)l-1-(3-((4-ethylphenyl)sulfonyl-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-amine 104

5-((3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4yl)amino)pentan-1-ol 105

3-((4-ethylphenyl)sulfonyl)-N-(piperidin-1-yl)-6-(trifluoromethoxy)quinolin-4-amine 106

3-((4-ethylphenyl)sulfonyl)-N-(pyridin-4-ylmethyl)-6-(trifluoromethoxy)quinolin-4-amine 107

3-((4-ethylphenyl)sulfonyl)-N-(pyridin-4-yl)-6-(trifluoromethoxy)quinolin-4-amine 108

3-((4-ethylphenyl)sulfonyl)-4-(1H-pyrrole-1-yl)-6-(trifluoromethoxy)quinoline109

3-((4-ethylphenyl)sulfonyl)-4-(1H-pylazol-1-yl)-6-(trifluoromethoxy)quinoline110

3-((4-ethylphenyl)sulfonyl)-4-(1H-1,2,3-triazol-1-yl)-6-(trifluoromethoxy)quinoline 111

4-((3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)amino)butan-1-ol 112

4-(1H-benzo[d][1,2,3]triazol-1-yl)-3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 113

1′-(3-((4-methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl-[1,4′-bipiperidin]-4-ol 114

4-([1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)-6-nitroquinoline 115

2-(4-([1,4′-bipiperidin]-1yl)-3-((4-methoxyphenyl)sulfonyl)quinolin-6-yl)acetonitrile 116

4-([1,4′-bipiperidin]-1′-yl)-6-butoxy-3-((3,4-dimethoxyphenyl)sulfonyl)quinoline 117

3-((4-ethylphenyl)sulfonyl)-4-(4-methyl-1H-imidazol-1-yl)-6-(trifluoromethoxy)quinoline 118

3-((4-ethylphenyl)sulfonyl)-4-(1H-imidazol-1-yl)-6-(trifluoromethoxy)quinoline 119

4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 120

4-([1,4′-bipiperidin]-1′-yl)-6-(trifluoromethoxy)-3-((4-(trifluoromethoxy)phenyl)sulfonyl)quinoline 121

4-([1,4′-bipiperidin]-1′-yl)-3-((3,4-dimethoxyphenyl)sulfonyl)-6-(methylthio)quinoline 122

4-([1,4′-bipiperidin]-1′-yl)-3-((3,4-dimethoxyphenyl)sulfonyl)-6,7-dimethoxyquinoline 123

6-butoxy-3-((3,4-dimethoxyphenyl)sulfonyl)-N,N-diethyl)lquinolin-4-amine124

N,N-dibutyl-3-((3,4-dimethoxyphenyl)sulfonyl)-6-(methythio)quinolin-4-amine 125

3-((4-ethylphenyl)sulfonyl)-4-(1H-tetrazol-1-yl)-6-(trifluorotmethoxy)quinoline 126

N-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)morpholin-4-amine 127

4-(4-ethylphenyl)-1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 128

ethyl 4-(4-(4-ethylphenyl)-4-hydroxypiperidin-1-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6-carboxylate 129

4-(4-ethylphenyl)-1-(3-((4-methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 130

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4-hydroxy-[1,4′-bipiperidin]-1′-yl)quinoline-6-carboxylate 131

ethyl 4-(4-(2-(diethyl)lamino)ethyl)-1,4-diazepan-1-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6-carboxylate 132

ethyl 4-(4-(2-(diethyl)laminotethoxy)piperidin-1-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6-carboxylate 133

ethyl 4-(1H-benzo[d][1,2,3]triazol-1-yl)-3-((4-ethylphenyl)sulfonyl)quinoline-6-carboxylate 134

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(1H-imidazol-1-yl)quinoline-6-carboxylate 135

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(3-hydroxypiperidin-1-yl)quinoline-6-carboxylate 136

ethyl 4-([1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 137

ethyl 4-(3-hydroxypiperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 138

ethyl 4-(4-hydroxy-[1,4′-bipiperidin]-1′-yl-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 139

ethyl4-(4-(2-(diethyl)lamino)ethyl)-1,4-diazepan-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate140

ethyl 4-(4-(2-(diethyl)lamino)ethoxy)piperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 141

ethyl 4-(1H-imidazol-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 142

ethyl 4-(1H-benzo[d][1,2,3]triazol-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 143

4-([1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl-N-methyl)quinoline-6-carboxamide 144

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxylate 145

1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-4-(4-methoxyphenyl)piperidin-4-ol146

1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-4-(3-methoxyphenyl)piperidin-4-ol147

4-(benzo[d][1,3]dioxol-5-yl)-1-(3-((4-ethylphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 148

ethyl 3-((4-ethylphenyl)sulfonyl)-4-(4-hydroxy-4-(4-methoxyphenylpiperidin-1-yl)quinoline-6-carboxylate 149

ethyl 3-((4-ethylphenyl)sulfonyl-4-(4-hydroxy-4-(3-methoxyphenyl)piperidin-1-yl)quinoline-6-carboxylate 150

4-(3-methoxyphenyl)-1-(3-((4-methoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)piperidin-4-ol 151

3-((4-butoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(trifluoromethoxy)quinoline 152

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)-[1,4′-bipiperidin]-4-ol153

1′-(3-((3,4-dimethoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-[1,4′-bipiperidin]-4-ol154

3-((3,4-dimethoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(methylthio)quinoline155

ethyl 4-(dibutylamino)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 156

ethyl 4-(bis(2-hydroxyethyl)amino)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 157

ethyl 4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)quinoline-6-carboxylate 158

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxylate 159

4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinoline 160

3-((4-butoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(methylthio)quinoline 161

ethyl3-((4-butoxyphenyl)sulfonyl)-4-(4-hydroxy-[1,4′-bipiperidin]-1yl)quinoline-6-carboxylate162

1′-(3-((4-butoxyphenyl)sulfonyl-6-(methylthio)quinolin-4-yl)-[1,4′-bipiperidin]-4-ol 163

3-((4-butoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(methylsulfinyl)quinoline 164

3-((4-butoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(methylsulfonyl)quinoline 165

N,N-diethyl)l-3-((4-methoxyphenyl)sulfonyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline-carboxamide 166

N-(2-(diethyl)lamino)ethyl)-3-((4-methoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 167

4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinoline 168

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-ol169

4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfonyl)quinoline 170

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfonyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-ol171

ethyl3-((4-methoxyphenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)quinoline-6-carboxylate172

ethyl3-((4-butoxyphenyl)sulfonyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)quinoline-6-carboxylate173

ethyl 4-(4-(azepan-1-yl)piperidin-1-yl)-3-((4-ethoxyphenyl)sulfonyl)quinoline-6-carboxylate 174

ethyl4-(3-hydroxy-[1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate175

ethyl 4-(4-(hydroxymethyl)-[1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxylate 176

ethyl 4-(4-(azepan-1-yl)piperidin-1-yl)-3-((4-butoxyphenyl)sulfonyl)quinoline-6-carboxylate 177

ethyl3-((4-butoxyphenyl)sulfonyl)-4-(3-hydroxy-[1,4′-bipiperidin]-1′-yl)quinoline-6-carboxylate178

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(hydroxymethyl)-[1,4′-bipiperidin]-1′-yl)quinoline-6-carboxylate 179

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline-6-carboxylate 180

ethyl3-((4-methoxyphenyl)sulfonyl)-4-(4-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline-6-carboxylate181

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline-6-carboxylate 182

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline-6-carboxylate 183

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinoline-6-carboxylate 184

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(1H-1,2,3-triazol-1-yl)quinoline-6-carboxylate 185

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-(1H-tetrazol-1-yl)quinoline-6-carboxylate 186

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-tetrazol-1-yl)quinoline-6-carboxylate 187

4-(3-((4-butoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)thiomorpholine 188

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinoline-6-carboxylate 189

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-1,2,3-triazol-1-yl)quinoline-6-carboxylate 190

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-1,2,4-triazol-1-yl)quinoline-6-carboxylate 191

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-thiomorpholinoquinoline-6-carboxylate 192

3-((4-butoxyphenyl)sulfonyl)-N-isopropyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 193

3-((4-butoxyphenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-N-((4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)quinoline-6-carboxamide 194

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1H-imidazol-1-yl)quinoline-6-carboxylate 195

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(1-oxidothiomorpholino)quinoline-6-carboxylate 196

ethyl3-((4-butoxyphenyl)sulfonyl)-4-(1,1-dioxidothiomorpholino)quinoline-6-carboxylate197

4-(3-((4-butoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)thiomorpholine 1-oxide 198

4-(3-((4-butoxyphenyl)sulfonyl)-6-(trifluoromethoxy)quinolin-4-yl)thiomorpholine 1,1-dioxide 199

3-((4-butoxyphenyl)sulfonyl)-N,N-diethyl)l-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide200

3-((4-butoxyphenyl)sulfonyl)-N-(2-hydroxyethyl)-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 201

4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)-N,N-diethyl)quinoline-6-carboxamide 202

4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)-N-(2-hydroxyethyl)quinoline-6-carboxamide 203

4-([1,4′-bipiperidin]-1′-yl)-3-((4-butoxyphenyl)sulfonyl)-N-ethyl)quinoline-6-carboxamide 204

4-(1H-imidazol-1-yl)-3-((4-methoxyphenyl)sulfonyl)-N-((4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)quinoline-6-carboxamide205

4-(1H-benzo[d][1,2,3]triazol-1-yl)-3-((4-methoxyphenyl)sulfonyl)-N-((4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)quinoline-6-carboxamide206

3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 207

3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)-4-(4-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 208

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-3-ol 209

3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline210

3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(pyrrolidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline211

ethyl3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)quinoline-6-carboxylate212

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-morpholinopiperidin-1-yl)quinoline-6-carboxylate 213

ethyl3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-fluorophenyl)piperazin-1-yl)quinoline-6-carboxylate214

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-(2-hydroxyethyl)piperazin-1-yl)piperidin-1-yl)quinoline-6-carboxylate 215

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-phenyl-[1,4′-bipiperidin]-1′-yl)quinoline-6-carboxylate 216

ethyl 4-([1,4′:1′,4″-terpiperidin]-1yl)-3-((4-butoxyphenyl)sulfonyl)quinoline-6-carboxylate 217

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-thiomorpholinopiperidin-1-yl)quinoline-6-carboxylate 218

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(methylthio)quinoline 219

4-([1,4′-bipiperidin]-1′-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 220

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-methyl-1,4-diazepan-1-yl)-6-(methylsulfinyl)quinoline 221

4-([1,4′-bipiperidin]-1′-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulflnyl)quinoline 222

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-[1,4′-bipiperidin]-3-ol 223

1′-(3-((4-(heplyloxy)phenyl)sulfonyl)-6-(methylthio)quinolin-4-yl-[1,4′-bipiperidin]-4-ol 224

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-ol 225

ethyl 3-((4-methoxyphenyl)sulfonyl)-4-((4-methylpiperazin-1-yl)amino)quinoline-6-carboxylate 226

3-((4-methoxyphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-(methylthio)quinolin-4-amine 227

3-((4-methoxyphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-(methylsulfinyl)quinolin-4-amine 228

3-((4-methoxyphenyl)sulfonyl)-N-(4-methylpiperazin-1-yl)-6-(methylsulfonyl)quinolin-4-amine 229

4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4-yl)morpholine 230

2-(4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan-1-ol 231

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinoline 232

1′-(3-((4-butoxyphenyl)sulfonyl-6-(methylthio)quinolin-4-yl)-4-phenyl-[1,4′-bipiperidin]-4-ol 233

3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-(4-fluorophenyl)piperazin-1-yl)piperidin-1-yl)-6-(methylthio)quinoline 234

3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)-6-(methylthio)quinoline235

4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)morpholine236

2-(4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan-1-ol237

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinoline 238

1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-4-phenyl-[1,4′-bipiperidin]-4-ol239

3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-(4-fluorophenyl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline240

(1′-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)methanol241

3-((4-butoxyphenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 242

N,N-diethyl)l-2-(4-((4-(4-methyl-1,4-diazepan-1-yl)-6-(methylthio)quinolin-3-yl)sulfonyl)phenoxy)ethan-1-amine 243

4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-piperidin-4-yl)thiomoroholine 244

ethyl 3-((4-butoxyphenyl)sulfonyl)-4-(4-(1-oxidothiomoroholino)piperidin-1-yl)quinoline-6-carboxylate 245

4-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)thiomorpholine 246

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-6-(methylthio)quinoline 247

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-[1,4′-bipiperidin]-3-ol 248

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 249

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)-6-(methylthio)quinoline 250

2-(4-(1-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan-1-ol 251

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 252

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-methylpiperazin-1-yl)-6-(methylthio)quinoline 253

3-((4-(heptyloxy)phenyl)sulfonyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 254

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl(-[1,4′-bipiperidin]-3-ol 255

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-1-yl)quinoline 256

3-((4-(heplyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quipoline 257

2-(4-(1-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan- 1-ol258

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 259

3-((4-heptyloxy)phenyl)sulfonyl)-4-(4-methylpiperazin-1-yl)-6-(methylsulfinyl)quinoline 260

3-((4-methoxyphenyl)sulfonyl)-4-((4-methylpiperazn-1-yl)amino)-N-((4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)quinoline-6-carboxamide 262

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-4-phenyl-[1,4′-bipiperidin]-4-ol 263

1′-(3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-4-phenyl-[1,4′-bipiperidin]-4-ol 264

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 265

1′-(3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-3-ol 266

3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(piperidin-1-yl)ethyl)-1,4-diazepan-l-yl)quinoline 267

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 268

2-(4-(1-(3-((4-(decyloxy)phenyl)sulfonyl-6-methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan-1-ol 269

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(decyloxy)phenyl)sulfonyl-6-(methylsulfinyl)quinoline 270

1′-(3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-4-phenyl-[1,4′-bipiperidin]-4-ol 271

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(4-(2-mPEGoxyethyl)piperazin-1-yl)piperidin-1-yl)-6-(methylthio)quinoline 272

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)-4-(4-(2-(pyrrolidin-1-yl)ethyl)piperazin-1-yl)quinoline 273

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)-6-(methylthio)quinoline 274

4-(4-(1-benzylpyrrolidin-3-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 275

4-(4-((1-benzylpiperidin-4-yl)methyl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 276

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(pyrrolidin-1-yl)ethyl)piperazin-1-yl)quinoline 277

4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 278

4-(4-(1-benzylpyrrolidin-3-yl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 279

4-(4-((1-benzylpiperidin-4-yl)methyl)piperazin-1-yl)-3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 280

3-((4-(heptyloxy)phenyl)sulfonyl)-4-(4-(4-(2-mPEGoxyethyl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl) quinoline281

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylthio)-4-(4-(2-(piperidin-1-yl)ethyl)piperazin-1-yl)quinoline 282

3-((4-(heptyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(2-(piperidin-1-yl)ethyl)piperazin-1-yl)quinoline 283

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)-6-(methylsulfinyl)quinoline 284

2-(4-(1-(3-((4-((3,7-dimethyloctyl)oxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan-1- ol285

3-((4-(decyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 286

4-(1′-(3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)morpholine 287

3-((4(decyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)-[1,4′-bipiperidin]-1yl)-6-(methylsulfinyl)quinoline 288

1″-(3-((4-(decyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl-[1,4′:1′,4″-terpiperidin]-3-ol 289

4-([1,4′:1,4″-terpiperidin]-1″-yl)-3-((4-((3,7-dimethyloctyl)oxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 290

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(decyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinoline 291

2-(4-(1-(3-((4-(decyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan- 1-ol292

2-(4-(1′-(3-((4-(decyloxy)phenyl)sulfonyl-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethan-1-ol 293

N,N-diethyl)l-6,7-dimethoxy-3-((4- methoxyphenyl)sulfonyl)quinolin-amine 294

N-ethyl-N-isopropyl-6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-amine 295

N,N-dibutyl-6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin- 4-amine296

N1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-N1,N2,N2-triethylethane-1,2-diamine 297

N1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-N2,N2-diethyl)lethane-1,2-diamine 298

N1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-N3,N3-diethyl)lpropane-1,3-diamine 299

N1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-N4,N4-diethyl)lbutane-1,4-diamine 300

N3-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-N1,N1-diethyl)lbutane-1,3-diamine 301

2-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperazin-1-yl)ethan-1-ol 302

3-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperazin-1-yl)-N,N-diethyl)lpropan-1-amine 303

1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-ol 304

(1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-3-yl)methanol 305

1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)pyrrolidin-3-ol 306

6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)-4-((1S,4S)-5-methyl-2,5-diazabicyclo[2,2,1]heptan-2-yl)quinoline 307

4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-N,N-dimethyl-1,4-diazepane-1-carboxamide 308

1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-4-phenylpiperidin-4-ol 309

methyl 4-(1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)benzoate 310

4-(1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)-N-methylbenzamide 311

6,7-dimethoxy-4-(4-(4-methoxyphenyl)piperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline 312

6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)-4-(4-(4-(pyrrolidin-1-ylmethyl)phenyl)piperidin-1-yl)quinoline 313

6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)-4-(3-phenylpyrrolidin-1-yl)quinoline 314

4-(3-(benzo[d][1,3]dioxol-5-yl)pyrrolidin-1-yl)-6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinoline 315

6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)-4-(4-phenylpiperazin-1-yl)quinoline 316

6,7-dimethoxy-4-(4-(4-methoxyphenyl)piperazin-1-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline 317

ethyl 4-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperazin-1-yl)benzoate 318

4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-1-(4-methoxyphenyl)piperazin-2-one 319

N-cyclohexyl-4-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperazin-1-yl)benzamide 320

4-([1,4′-bipiperidin]-1′-yl)-6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinoline 321

1-(1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)pyrrolidin-2-one 322

(1-(1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)pyrrolidin-2-yl)methanol 323

2-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-1,4-diazepan-1-yl)ethan-1-ol 324

7-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-1-isobutyldecahydropyrido[4,3-e][1,4]oxazepine 325

1-((4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-1,4-diazepan-1-yl)methyl)cyclopentan-1-ol 326

6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)-4-(4-(oxelan-3-yl)-1,4-diaxepan-1-yl)quinoline 327

6-chloro-2-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-1,4-diazepan-1-yl)benzo[d]thiazole 328

1-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-4-methyl-1,4-diazepan-5-one 329

6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)-4-(4-(tetrahydro-2H-thiopyran-4-yl)-1,4-diazepan-1-yl)quinoline 330

4-(4-(6,7-dimethoxy-3-((4-methoxyphenyl)sulfonyl)quinolin-4-yl)-1,4-diazepan-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide 331

4-([1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)-N,N-dimethylquinoline-6-carboxamide 332

3-((4-methoxyphenyl)sulfonyl)-N,N-dimethyl-4-(4-(2-oxopyrrolidin-1-yl)piperidin-1-yl)quinoline-6-carboxamid 333

4-(4-(2-(dimethylamino)-2-oxoethyl)-1,4-diazepan-1-yl)-3-((4-methoxyphenyl)sulfonyl)-N,N-dimethyl)quinoline-6-carboxamide 334

4-([1,4′-bipiperidin]-1′-yl)-3-((4-methoxyphenyl)sulfonyl)-N-methylquinoline-6-carboxamide 335

3-((4-methoxyphenyl)sulfonyl)-N-methyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 336

4-(4-(2-(hydroxymethyl)pyrrolidin-1-yl)piperidin-1-yl)-3-((4-methoxyphenyl)sulfonyl)-N-methylquinoline-6-carboxamide 337

4([1,4′-bipiperidin]-1′-yl(-N-(2-(diethyl)lamino)ethyl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxamide 338

N-(2-(diethyl)lamino)ethyl)-4-(1-isobutyloctahydropyrido[4,3-e][1,4]oxazepin-7(5H)-yl)-3-((4-methoxyphenyl)sulfonyl)quinoline-6-carboxamide 339

2-(4-(1-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan-1-ol 340

2-(4-(1′-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethan-1-ol 341

3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 342

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 343

1″-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 344

2-(4-(1-(6-(methylsulfinyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethan-1-ol 345

2-(4-(1′-(6-(methylsulfinyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethan-1-ol 346

4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinoline 347

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-6-(methyl(λ¹-oxidanyl)-λ³-sulfanyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinoline 348

1″-(6-(methyl(λ¹-oxidanyl)-λ³-sulfanyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′:1,4″-terpiperidin]-3-ol 349

1-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4-yl)pyrrolidin-2-one 350

(1-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4-yl)pyrrolidin-2-yl)methanol 351

2-(4-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-1,4-diazepan-1-yl)ethan-1-ol 352

7-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-1-isobutyldecahydropyrido[4,3-e][1,4]oxazepine 353

4-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-N-(2,2,2-trifluoroethyl)-1,4-diazepane-1-sulfonamide 354

1-((4-(3-((4-butoxyphenyl)sulfonyl-6-(methylthio)quinolin-4-yl)-1,4-diazepan-1-yl)methyl)cyclopentan-1-ol 355

3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)-4-(4-(oxelan-3-yl)-1,4-diazepan-1-yl)quinoline 356

2-(4-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-1,4-diazepan-1-yl)-6-chlorobenzo[d]thiazole 357

1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-4-methyl-1,4-diazepan-5-one 358

3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)-4-(4-(tetrahydro-2H-thiopyran-4-yl)-1,4-diaxepan-1-yl)quinoline 359

4-(4-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)-1,4-diazepan-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide 360

3-((4-methoxyphenyl)sulfonyl)-N-methyl-4-methylamino)quinoline-6-carboxamide 361

1-(1-(3-((4-butoxyphenyl)sulfonyl)-6-(methylthio)quinolin-4-yl)piperidin-4-yl)pyrrolidin-2-one 362

2-(4-(1-(3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethanol 363

4-([1,4′:1,4″-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinoline 364

1″-(3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 365

2-(4-(1-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin- 1-yl)ethanol 366

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((3-fluoro-4-(tetradecyloxy)phenylsulfonyl)-6-(methylsulfinyl)quinoline 367

1″-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 368

2-(4-(1′-(3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 369

2-(4-(1′-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 370

3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 371

3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 372

1″-(3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl-[1,4′:1′,4″-terpiperidin]-4-ol 373

1″-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-4-ol 374

1″-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-4-ol 375

1″-(6-(methylsulfinyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-4-ol 376

2-(4-(1-(3-((4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethanol377

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 378

1″-(3-((4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 379

3-((4-methoxyphenyl)sulfonyl)-N,N-dimethyl-4-(4-methyl-1,4-diazepan-1-yl)quinoline-6-carboxamide 380

2-(4-(1-(6-(methylsulfinyl)-3-((4-(undecyloxy)phenyl)sulfonyl)quinolin-4-yl)piperidin-4-yl)piperazin-1-yl)ethanol 381

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-6-(methylsulfinyl)-3-((4-(undecyloxy)phenyl)sulfonyl)quinoline 382

1″-(6-(methylsulfinyl)-3-((4-(undecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4,:1′,4″-terpiperidin]-4-ol 383

1″-(6-(methylsulfinyl)-3-((4-(undecyloxy)phenyl)sulfonyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 384

2-(4-((4-([1,4′:1′,4″-terpiperidin]-1″-yl)-6-(methylsulfinyl)quinolin-3-yl)sulfonyl)phenoxy)-N,N-diethyl)lethanamine 385

2-(4-(1′-(3-((4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)pipeiazin-1-yl)ethanol 386

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 387

2-(4-(1′-(3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 388

3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 389

1′-(3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 390

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 391

3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 392

3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methyl-1,4-diazepan-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 393

4-(1′-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)quinoline 394

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 395

3-((2-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 396

3-((3,5-difluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 397

3-((2,3-difluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 398

4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl) quinoline 399

3-((3-fluoro-4-(octadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 400

4-(1′-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4- yl)thiomorpholine401

1-(4-(1′-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-ylethanone 402

3-((3-fluoro-4-(tetradecyloxylphenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfonyl)quinoline 403

(S)-1″-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-((S)-methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 404

(S)-1″-(3-((4-(dodecyloxy)phenyl)sulfollyl)-6-((R)-methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 405

(R)-1″-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-((S)-methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 406

(R)-1″-(3-((4-(dodecyloxy)phenyl)sulfonyl)-6-((R)-methylsulfinyl)quinolin-4-yl)-[1,4′:1′,4″-terpiperidin]-3-ol 407

(R)-2-(4-(1′-(3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazn-1-yl)ethanol 408

(S)-2-(4-(1′-(3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 409

(R)-2-(4-(1′′-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 410

(S)-2-(4-(1′-(3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinolin-4-yl)-[1,4′-bipiperidin]-4-yl)piperazin-1-yl)ethanol 411

3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 412

3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-4-(4-(4-isopropylpipeiazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 413

3-((4-(dodecyloxy)-3-fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 414

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6(methylsulfinyl)quinoline 415

3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 416

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 417

3-((4-(dodecyloxy)-2,3-difluorophenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 418

3-((4-(dodecyloxy)-2,3-difluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 419

3-((4-(dodecyloxy)-2,3-difluorophenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 420

3-((4-(dodecyloxy)-2,3-difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 421

3-((2,3-difluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 422

3-((2,3-difluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 423

3-((2,3-difluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 424

3-((2,3-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 425

3-((2,3-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 426

3-((2,3-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1yl)-6-(methylsulfinyl)quinoline 427

3-((2,3-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpipendin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 428

3-((4-(dodecyloxy)-3,5-difluorophenyl)sulfonyl)-4-(4-(4-methylpiperazn-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 429

3-((4-(dodecyloxy)-3,5-difluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 430

3-((4-(dodecyloxy)-3,5-di1′luorophenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 431

3-((4-(dodecyloxy)-3,5-difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 432

3-((3,5-difluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazn-1-yl-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 433

3-((3,5-difluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 434

3-((3,5-difluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)pipeiaxip-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 435

3-((3,5-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 436

3-((3,5-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 437

3-((3,5-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 438

3-((3,5-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 439

3-((4-(dodecyloxy)-2-fluorophenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 440

3-((4-(dodecyloxy)-2-fluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 441

3-((4-(dodecyloxy)-2-fluorophenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 442

3-((4-(dodecyloxy)-2-fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 443

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((2-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 444

3-((2-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 445

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6- methylsulfinyl)quinoline446

3-((2-fluoro-4-(hexadecyloxy)phenyl)sulfonyl-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 447

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((2-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 448

3-((2-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 449

4-(4-(4-(1-ethylpiperidin-4-yl)piperazn-1-yl)piperidin-1-yl)-3-((2-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline 450

4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)-2,3-difluorophenyl)sulfonyl-6-(methylsulfinyl)quinoline 451

3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 452

3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 453

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinoline 454

4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(tetradecyloxy)phenyl)sulfonyl)quinoline 455

(R)-4-(4-(4-methylpiperazn-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 456

(S)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 457

(R)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 458

(S)-4-(4-(4-ethylpiperazn-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 459

(R)-4-(4-(4-cyclopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 460

(S)-4-(4-(4-cyclopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 461

3-((4-(icosyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 462

4-(4-(4-ethylpiperazin-1-yH-[1,4′-bipiperidin]-1′-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 463

(R)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 464

(S)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 465

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 466

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazn-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 467

(R)-3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 468

(S)-3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl-6-(methylsulfinyl)quinoline 469

(R)-3-((4-(dodecyloxy)-2,3-difluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 470

(S)-3-((4-(dodecyloxy)-2,3-difluorophenyl)sulfonyl)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 471

(R)-4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline472

(S)-4-(4-(4-ethylpiperazin-1-yl-[1,4′-bipiperidin]-1′-yl-3-((3-fluoro-4-(tetradecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 473

(R)-3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 474

(S)-3-((4-(dodecyloxy)phenyl)sulfonyl)-4-(4-(4-isopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsutriny)quinoline 475

(R)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 476

(S)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)quinoline 477

(R)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 478

(S)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 479

(R)-4-([1,4′:1′,4′′-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 480

(S)-4-([1,4′:1′,4″-terpiperidin]-1″-yl)-3-((4-(dodecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 481

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylthio)quinoline 482

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfonyl)quinoline 483

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 484

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 485

(R)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfonyl)quinoline 486

(S)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfonyl)quinoline 487

(R)-3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 488

(S)-3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 489

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfinyl)-3-((4-(tetracosyloxy)phenyl)sulfonyl)quinoline 490

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)-3-((4-(tetracosyloxy)phenyl)sulfonyl)quinoline 491

4-(4-(4-ethylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((4-(hexacosyloxy)phenyl)sulfonyl)-6-(methylsulfonyl)quinoline 492

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(hexacosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 493

3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(4-propylpiperazin-1-yl-[1,4′-bipiperidin]-1′-yl)quinoline 494

4-(4-(4-butylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 495

3-((4-(docosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)-4-(4-(4-propylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)quinoline 496

4-(4-(4-butylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl-3-((4-(docosyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 497

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylthio)quinoline 498

3-((4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-methylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-6-(methylsulfonyl)quinoline 499

4-(4-(4-(1-ethylpiperidin-4-yl)piperazn-1-yl)piperidin-1-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 500

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylsulfinyl)quinoline 501

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6-methoxyquinoline 502

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(hexadecyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 503

4-(4-(4-(1-ethylolneridin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 504

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline505

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6-methoxyquinoline 506

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 507

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylthio)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 508

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 509

4-(4-(4-(1-ethylolneridin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-methoxy-3-((4-(octadecyloxy)phenyl)sulfonyl)quinoline 510

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(octadecyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 511

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(octadecyloxy)phenyl)sulfonyl)-6-methylthio)quinoline 512

4-(4-(4-(1-ethylolneridin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(octadecyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline513

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(octadecyloxy)phenyl)sulfonyl)-6-methoxyquinoline 514

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(octadecyloxy)phenyl)sulfonyl)-6-methoxyquinoline 515

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylthio)quinoline 516

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(methylsulfiny)quinoline 517

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-methoxyquinoline 518

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((4-(icosyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 519

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(icosyloxy)phenyl)sulfonyl-6-(methylthio)quinoline 520

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(icosyloxy)phenyl)sulfonyl)-6- (methylsulfinyl)quinoline521

4-(4-(4-(1-ethylolneridin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(icosyloxy)phenyl)sulfonyl)-6-methoxyquinoline 522

4-(4-(4-(I-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((3-fluoro-4-(icosyloxy)phenyl)sulfonyl)-6- (trifluoromethoxy)quinoline523

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylthio)quinoline 524

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfonyl)quinoline 525

3-((4-(docosyloxy)phenyl)sulfonyl-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-methoxyquinoline 526

3-((4-(docosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 527

3-((4-(docosyloxy)-3-fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylthio)quinoline 528

3-((4-(docosyloxy)-3-fluorophenyl)sulfonyl-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(methylsulfinyl)quinoline 529

3-((4-(docosyloxy)-3-fluorophenyl)sulfonyl-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6- methoxyquinoline530

3-((4-(docosyloxy)-3-fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 531

3-((4-(docosyloxy)-3,5-difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 532

3-((4-(docosyloxy)-2,3-difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 533

3-((4-(docosyloxy)-2-fluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 534

3-((3,5-difluoro-4-(icosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 535

3-((2,3-difluoro-4-(icosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 536

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4-(icosyloxy)phenyl)sulfonyl)-6- (trifluoromethoxy)quinoline 537

3-((3,5-difluoro-4-(octadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 538

3-((2,3-difluoro-4-(octadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 539

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4-(octadecyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 540

3-((3,5-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 541

3-((2,3-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 542

4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-3-((2-fluoro-4-(hexadecyloxy)phenyl)sulfonyl)-6-(trifluoromethoxy)quinoline 543

3-((2,6-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 544

3-((2,6-difluoro-4-(octadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 545

3-(42,6-difluoro-4-(icosyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 546

3-((4-(docosyloxy)-2,6-difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 547

3-((2,5-difluoro-4-(hexadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 548

3-((2,5-difluoro-4-(octadecyloxy)phenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline 549

3-((2,5-difluoro-4-(icosyloxy)phenyl)sulfonyl-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline and 550

3-((4-(docosyloxy)-2,5-difluorophenyl)sulfonyl)-4-(4-(4-(1-ethylpiperidin-4-yl)piperazin-1-yl)piperidin-1-yl)-6-(trifluoromethoxy)quinoline

or a pharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof.
 60. Apharmaceutical composition comprising a compound of claim 13 or apharmaceutically acceptable salt, isotopically enriched analog,stereoisomer, mixture of stereoisomers, or tautomer thereof. 61.-62.(canceled)
 63. A method of agonizing Pigment-Epithelium-Derived Factor(PEDF) receptors in a patient in need thereof, comprising administeringto the patient an effective amount of a compound of claim
 13. 64. Amethod of inhibiting angiogenesis in a patient in need thereof,comprising administering to the patient an effective amount of acompound of claim
 13. 65. (canceled)
 66. A method treating a pathogenicblood vessel-related disorder in a patient in need thereof, comprisingadministering to the patient an effective amount of a compound of claim13.
 67. (canceled)
 68. A method of treating a cancer in a patient inneed thereof, comprising administering to the patient an effectiveamount of a compound of claim
 13. 69. (canceled)
 70. A method oftreating retinal occlusive vascular disease or retinopathy ofprematurity in a patient in need thereof, comprising administering tothe patient an effective amount of a compound of claim
 13. 71. A methodof treating diabetic retinopathy in a patient in need thereof,comprising administering to the patient an effective amount of acompound of claim
 13. 72. A method of treating age-related maculardegeneration in a patient in need thereof, comprising administering tothe patient an effective amount of a compound of claim 13.